On May 19, 2021 SQZ Biotechnologies Company (NYSE: SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, reported that it will present safety and tolerability, manufacturing, and antitumor activity data from its ongoing Phase 1 clinical trial of SQZ-PBMC-HPV-101 in patients with advanced or metastatic Human Papillomavirus Positive tumors at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8 (Press release, SQZ Biotech, MAY 19, 2021, View Source [SID1234580309]).

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"These early data demonstrate the feasibility of our Cell Squeeze technology and how it can potentially change the way the field thinks about cell therapies," said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. "In this small number of patients whose cancer was very advanced, SQZ-PBMC-HPV-101 has been well-tolerated at all tested dose levels and demonstrated signals of increased immune activity. Importantly, we are also presenting evidence that we can efficiently and reproducibly manufacture our investigational therapy at scale, potentially making it more accessible to patients in need."

The Phase 1 clinical trial data of SQZ-PBMC-HPV-101 being presented at ASCO (Free ASCO Whitepaper) includes three of the four planned monotherapy dose-escalating patient cohorts. Enrollment and evaluation of the monotherapy in the highest-dose cohort is ongoing. In the next stage of the trial, it is planned to combine SQZ-PBMC-HPV-101 with immune checkpoint inhibitors. The study’s primary outcome measures in the monotherapy stage of the trial are safety, tolerability, and the definition of the recommended phase 2 dose. Secondary outcome measures include antitumor activity and manufacturing feasibility.

Trial Highlights from ASCO (Free ASCO Whitepaper) Abstract 2536

Design, Safety, Tolerability and Patient Demographics

SQZ-PBMC-HPV was given IV q 3 weeks on an outpatient basis and patients did not receive a prior conditioning regime
The median number of lines of prior therapy was four, and all but one patient had previously received an immune checkpoint inhibitor
SQZ-PBMC-HPV-101 was well-tolerated at all dose levels tested with patients receiving between two to 10 doses
No dose-limiting toxicity or Grade 3 or higher treatment-related SAEs were observed
Manufacturing

All batches of SQZ-PBMC-HPV-101 demonstrated HPV-specific CD8 T cell activation in vitro after thawing, and batch size allowed for treatment at the assigned dose regimen
Quick and efficient manufacturing with all patient batches produced in less than 24 hours
Investigational doses were released and available for administration approximately one week from the time a patient’s cells were drawn
Outcome and Biomarker

Four patients achieved stable disease
One patient who achieved stable disease remained on study for 42 weeks
Preliminary analyses on pre- and post-therapy tumor biopsies indicated increased immune activity in select patients
Poster Presentation Details

Title: Initial Results of a first-in-human, dose escalation study of a cell-based vaccine in HLA A* 02+ patients with recurrent, locally advanced or metastatic HPV16+ solid tumors

First Author: Antonio Jimeno, M.D., Ph.D., University of Colorado Cancer Center

Abstract Number: 2536

Poster Session: Developmental Therapeutics — Immunotherapy

Date and Time: A copy of the poster will be available on-demand starting Friday, June 4, 2021 at 8:00 am ET via the ASCO (Free ASCO Whitepaper) virtual meeting website.

SQZ-PBMC-HPV-101 Trial Design

SQZ-PBMC-HPV-101 is being evaluated in a Phase 1 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A-*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination stages of the trial include safety, tolerability, and to define a recommended phase 2 dose. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy stage of the trial. The monotherapy phase of the study includes escalating dose cohorts with DLT measured over 28 days. The planned safety combination phase of the study will include SQZ-PBMC-HPV-101 and checkpoint inhibitors that have previously received regulatory approval. DLT will be measured over 42 days in the safety combination phase.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On May 19, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported updated data from the Phase 1/2 trial of mobocertinib (TAK-788) orally administered in patients with epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive (insertion+) metastatic non-small cell lung cancer (mNSCLC) who received prior platinum-based chemotherapy (Press release, Takeda, MAY 19, 2021, View Source [SID1234580308]). The results showed mobocertinib continued to demonstrate clinically meaningful benefit after over a year of follow up and will be presented at the virtual 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4.

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"Patients with EGFR Exon20 insertion+ mNSCLC have no proven targeted therapy options," said Suresh S. Ramalingam, MD, Deputy Director of Winship Cancer Institute of Emory University. "The updated results from the Phase 1/2 study of mobocertinib demonstrate an encouraging objective response rate, duration of response and overall survival in patients who have received prior platinum-based chemotherapy."

The analysis from the Phase 1/2 trial included patients with EGFR Exon20 insertion+ mNSCLC who received prior platinum-based chemotherapy. All patients were treated at the 160 mg once daily oral dose. Building on the findings presented in January at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC), results showed a median overall survival (OS) of 24 months with a median follow up of 14 months, and responses were observed across diverse EGFR Exon20 insertion variants. Other key data points remained consistent with previously reported data, including a confirmed objective response rate (ORR) of 28%, a median duration of response (DoR) of 17.5 months and a disease control rate (DCR) of 78% per independent review committee (IRC).

The safety profile observed was manageable and consistent with previous findings. The most common treatment-related adverse events (TRAEs; ≥ 20%) in platinum-pretreated patients from the updated data were diarrhea (91%), rash (45%), paronychia (38%), decreased appetite (35%), nausea (34%), dry skin (31%) and vomiting (30%). The only Grade ≥3 TRAE (≥5%) was diarrhea (21%). AEs leading to discontinuation in >2% were diarrhea (4%) and nausea (4%).

"We are excited to add this promising overall survival data to the body of evidence demonstrating mobocertinib’s potential as an effective oral treatment option for platinum-pretreated patients with EGFR Exon20 insertion+ mNSCLC," said Christopher Arendt, PhD, Head, Oncology Therapeutic Area Unit, Takeda. "Mobocertinib is currently undergoing priority review with the U.S. FDA, and we look forward to continuing conversations with regulatory agencies around the world to introduce mobocertinib as a new treatment option for these patients."

The FDA previously granted mobocertinib Breakthrough Therapy Designation in April 2020 and priority review for the New Drug Application (NDA) in April 2021. If approved, mobocertinib will be the first oral therapy available that is specifically designed to selectively target EGFR Exon20 insertion mutations.

Takeda has established an Expanded Access Program (EAP) for patients who may be eligible to receive access to mobocertinib while this investigational therapy is under review by regulatory authorities. Additional information, including the specific conditions to qualify for Takeda’s EAP, is available here.

Learn more about Takeda Oncology’s presence at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting. Takeda will host a webcast for analysts and investors on Tuesday, June 8, at 6:30 p.m. ET to discuss these and other data being presented at ASCO (Free ASCO Whitepaper) and to provide an update on the oncology pipeline. Please contact [email protected] for further details. Presentation slides and an archived replay of the webcast will be available at View Source

About Mobocertinib (TAK-788)

Mobocertinib is an investigational, first-in-class, oral tyrosine kinase inhibitor (TKI) specifically designed to selectively target epidermal growth factor receptor (EGFR) Exon20 insertion mutations. In 2019, the U.S. FDA granted mobocertinib Orphan Drug Designation for the treatment of lung cancer with HER2 mutations or EGFR mutations including Exon20 insertion mutations. In April 2020, mobocertinib received Breakthrough Therapy Designation from the FDA for patients with EGFR Exon20 insertion+ metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after platinum-based chemotherapy. In October 2020, mobocertinib was designated as a Breakthrough Therapy in China by the Center for Drug Evaluation (CDE) for locally advanced or metastatic NSCLC patients with EGFR Exon20 insertion mutations who have been previously treated with at least one prior systemic chemotherapy.

About the Phase 1/2 Trial

The Phase 1/2 trial evaluated the safety, pharmacokinetics and anti-tumor activity of oral mobocertinib in patients with non-small cell lung cancer (NSCLC). The trial is comprised of a Phase 1 dose-escalation, which evaluated mobocertinib as a monotherapy and in combination with chemotherapy, several expansion cohorts and an extension cohort in patients with epidermal growth factor receptor (EGFR) Exon20 insertion+ metastatic NSCLC (mNSCLC).

The platinum-pretreated population efficacy analysis investigated 114 patients with EGFR Exon20 insertion+ mNSCLC who received prior platinum-based therapy in the Phase 1/2 trial and were treated with mobocertinib at the 160 mg once daily dose.

About EGFR Exon20 Insertion+ mNSCLC

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.1,2 Patients with epidermal growth factor receptor (EGFR) Exon20 insertion+ metastatic NSCLC (mNSCLC) make up approximately 1-2% of patients with NSCLC, and the disease is more common in Asian populations compared to Western populations.3-7 This disease carries a worse prognosis than other EGFR mutations because there are currently no FDA-approved therapies that target EGFR Exon20 insertions, and current EGFR TKIs and chemotherapy provide limited benefit for these patients.

Takeda is committed to continuing research and development in EGFR Exon20 insertion+ mNSCLC with the hope of introducing a targeted treatment option for the approximately 30,000 patients diagnosed with the disease worldwide each year, including 3,000 in the U.S. alone.3,4

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

On May 19, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that primary analysis data from the Phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial will be presented during an oral session at the virtual 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and as an oral session at the virtual 26th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting (Press release, Takeda, MAY 19, 2021, View Source [SID1234580307]). The OPTIC trial is a randomized, open-label study prospectively evaluating response-based dosing regimens of ICLUSIG (ponatinib) over a range of three starting doses (45-, 30-, or 15-mg) with the aim of optimizing its efficacy and safety in patients with chronic-phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy.

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"The OPTIC data, along with the recently updated U.S. FDA indication, demonstrate the benefit ICLUSIG can offer as a third-generation TKI."

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The OPTIC trial, which evaluated treatment in patients with resistant disease, with and without mutations, met its primary endpoint. The study demonstrates that the optimal benefit-risk profile for ICLUSIG in patients with CP-CML is achieved with a daily starting dose of 45-mg and, upon achieving ≤1% BCR-ABL1IS, dose reduction to 15-mg. The results also suggest a clinically manageable safety and arterial occlusive event (AOE) profile for ICLUSIG.

"The primary analysis of the OPTIC data reinforce that ICLUSIG is very valuable in the management of patients with resistant and intolerant chronic-phase CML. ICLUSIG should be considered following failure of two or more TKIs. This approach minimizes the need to use back-to-back second-generation TKIs, which is usually associated with low probability of response and poor outcomes," said Jorge Cortes, MD, Georgia Cancer Center at Augusta University, and an OPTIC trial principal investigator. "These findings further demonstrate that the optimal ICLUSIG benefit-risk profile can be achieved with a response-based dosing regimen, providing efficacy while reducing risk for arterial occlusive events."

The first presentation of OPTIC data at the 56th ASCO (Free ASCO Whitepaper) and the 25th EHA (Free EHA Whitepaper) virtual Annual Meetings in 2020 showcased revised benefit-risk outcomes of ICLUSIG from the interim analysis (cutoff date of July 2019), which evaluated 216 patients with a median follow-up of 21 months. The primary analysis evaluated 283 patients with a median follow-up time of 32 months, reinforcing the positive and prolonged duration of response in this resistant CP-CML patient population while maintaining a manageable safety profile at a longer follow-up period.

"There is a misconception that chronic-phase CML is a ‘good cancer’ due to the fact it can be well controlled, but for patients with resistant and intolerant disease, continued investigation and treatment options are critical. The primary analysis of OPTIC solidifies our understanding of how ICLUSIG can address gaps in care for these patients," said Christopher Arendt, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. "The OPTIC data, along with the recently updated U.S. FDA indication, demonstrate the benefit ICLUSIG can offer as a third-generation TKI."

In December 2020, the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for ICLUSIG based on the OPTIC data. The updated label includes an expanded indication for adult patients with CP-CML that is resistant or intolerant to at least two prior kinase inhibitors, as well as the optimized response-based dosing regimen.

OPTIC Primary Analysis: A Dose-Optimization Study of Three Starting Doses of Ponatinib (PON).

Key findings, to be presented by Dr. Jorge Cortes, include:

By the primary analysis (cutoff date of May 2020) with median follow-up time of 32 months, 100% of patients in the OPTIC trial were evaluable for the primary endpoint.
The maximum rates of ≤1% BCR-ABL1IS at 12 months were achieved in the 45-mg/day starting dose cohort (44.1%), and 73.3% of patients in this cohort maintained responses with the dose reduction to 15-mg/day. 30-mg/day and 15-mg/day cohorts also demonstrated benefit (29% and 23%, respectively), especially in patients with less-resistant disease and without the T315I mutation.
Positive survival outcomes were observed in all three arms, with an 89% 36-month overall survival (OS) probability anticipated for the 45-mg starting dose cohort and 73% progression-free survival (PFS) anticipated for the same cohort.
This indicates the dose-reduction strategy did not impact overall survival regardless of prior second-generation TKI resistance or the presence of BCR-ABL1 mutations.
Rates of arterial occlusive events (AOEs) observed at the time of primary analysis (6% overall and 9.6% in the 45-mg cohort) suggest a clinically manageable safety and AOE profile.
Safety data include:
Among all patients (N=283), the most common treatment emergent adverse events (TEAEs) Grade 3 or greater were thrombocytopenia (27%), neutropenia (17%) and anemia (7%).
Reported AOEs were 10%, 5% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively. Grade 3 or greater AOEs were 5%, 5% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively.
Reported serious AOEs were 4%, 4% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively. There were 4 deaths related to AEs (2 sudden deaths and 2 pneumonia).
Learn more about Takeda Oncology’s presence at this year’s ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) annual meetings. Takeda will host a webcast for analysts and investors on Tuesday, June 8, at 6:30 p.m. ET to discuss these and other data being presented at ASCO (Free ASCO Whitepaper), and to provide an update on the oncology pipeline. Please contact [email protected] for further details. Presentation slides and an archived replay of the webcast will be available at View Source

About the OPTIC Trial

OPTIC (Optimizing Ponatinib Treatment In CML) is an ongoing randomized, dose-ranging trial designed to evaluate three starting doses of ICLUSIG (45-, 30-, and 15-mg) in patients with resistant chronic-phase chronic myeloid leukemia (CP-CML) or who had documented history of presence of T315I mutation after receiving any number of prior TKIs. Dose reduction at response occurred per study protocol. The trial is expected to inform the optimal use of ICLUSIG (ponatinib) in these patients. 282 patients were enrolled at clinical sites around the world, with 94 patients receiving the 45-mg starting dose. The primary endpoint of the trial is achieving ≤1% BCR-ABL1IS at 12 months.

OPTIC data showed that optimal benefit-risk with ICLUSIG can be obtained with a response-based dosing regimen, 45-mg/day to 15-mg/day upon achieving ≤1% BCR-ABL1IS in patients with CP-CML highly resistant to prior TKI therapies both with or without mutations. At 12 months, 44% (41/93) of patients who received the 45-mg starting dose achieved ≤1% BCR-ABL1IS. At a median follow up time of 32 months, the OPTIC study showed that, among patients receiving ICLUSIG 45- to 15-mg, 73% maintained their response. In these patients, 10% experienced an AOE of any Grade, 5% experienced Grade 3 or higher. The most common TEAEs occurring in > 15% of patients were thrombocytopenia, hypertension, headache, neutropenia, anemia, headache, lipase increased, alanine aminotransferase (ALT) increased, and arthralgia.

About CML and Ph+ ALL

CML – a rare malignancy – is one of four main types of leukemia; it is a result of a genetic mutation that takes place in early, immature versions of myeloid cells, which form red blood cells, platelets and most types of white blood cells. Subsequently, an abnormal gene called BCR-ABL1 forms, turning the damaged cell into a CML cell. CML typically progresses slowly, but it can change into a fast-growing acute leukemia that is hard to treat.

Ph+ ALL is a rare form of ALL that affects approximately 25% of adult ALL patients in the U.S. and is characterized by the presence of an abnormal gene, known as the Philadelphia chromosome. In patients who are Philadelphia chromosome-positive (Ph+), an abnormal chromosome is formed when pieces of chromosomes 9 and 22 switch with each other. This forms a longer chromosome 9 and a shorter chromosome 22, which leads to the development of BCR-ABL1 and is associated with Ph+ ALL.

About ICLUSIG (ponatinib) tablets

ICLUSIG is a kinase inhibitor targeting BCR-ABL1, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL. ICLUSIG is a targeted cancer medicine developed using a computational and structure-based drug-design platform, specifically designed to inhibit the activity of BCR-ABL1 and its mutations. ICLUSIG inhibits native BCR-ABL1, as well as all BCR-ABL1 treatment-resistant mutations, including the most resistant T315I mutation. ICLUSIG is the only approved TKI that demonstrates activity against the T315I gatekeeper mutation of BCR-ABL1. This mutation has been associated with resistance to all other approved TKIs. ICLUSIG received full approval from the FDA in November 2016. ICLUSIG is indicated for the treatment of adult patients with chronic-phase (CP) CML with resistance or intolerance to at least two prior kinase inhibitors, accelerated-phase (AP) or blast-phase (BP) CML or Ph+ ALL for whom no other kinase inhibitor is indicated, and T315I+ CML (CP, AP or BP) or T315I-positive Ph+ ALL. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

IMPORTANT SAFETY INFORMATION

WARNING: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning.

Arterial occlusive events (AOEs), including fatalities, have occurred in ICLUSIG-treated patients. AOEs included fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Monitor for evidence of AOEs. Interrupt or discontinue ICLUSIG based on severity. Consider benefit-risk to guide a decision to restart ICLUSIG.
Venous thromboembolic events (VTEs) have occurred in ICLUSIG-treated patients. Monitor for evidence of VTEs. Interrupt or discontinue ICLUSIG based on severity.
Heart failure, including fatalities, occurred in ICLUSIG-treated patients. Monitor for heart failure and manage patients as clinically indicated. Interrupt or discontinue ICLUSIG for new or worsening heart failure.
Hepatotoxicity, liver failure and death have occurred in ICLUSIG-treated patients. Monitor liver function tests. Interrupt or discontinue ICLUSIG based on severity.
WARNINGS AND PRECAUTIONS

Arterial Occlusive Events (AOEs): AOEs, including fatalities, have occurred in patients who received ICLUSIG in OPTIC and PACE. These included cardiovascular, cerebrovascular, and peripheral vascular events. The incidence of AOEs in OPTIC (45 mg→15 mg) was 13% of 94 patients; 5% experienced Grade 3 or 4. In PACE, the incidence of AOEs was 26% of 449 patients; 14% experienced Grade 3 or 4. Fatal AOEs occurred in 2.1% of patients in OPTIC, and in 2% of patients in PACE. Some patients in PACE experienced recurrent or multisite vascular occlusion. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. The most common risk factors observed with these events in PACE were history of hypertension, hypercholesterolemia, and non-ischemic cardiac disease. In OPTIC and PACE, AOEs were more frequent with increasing age.

In OPTIC, patients with uncontrolled hypertension or diabetes and patients with clinically significant, uncontrolled, or active cardiovascular disease were excluded. In PACE, patients with uncontrolled hypertriglyceridemia and patients with clinically significant or active cardiovascular disease within the 3 months prior to the first dose of ICLUSIG were excluded. Consider whether the benefits of ICLUSIG are expected to exceed the risks.

Monitor for evidence of AOEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity. Consider benefit-risk to guide a decision to restart ICLUSIG.

Venous Thromboembolic Events (VTEs): Serious or severe VTEs have occurred in patients who received ICLUSIG. In PACE, VTEs occurred in 6% of 449 patients including serious or severe (Grade 3 or 4) VTEs in 5.8% of patients. VTEs included deep venous thrombosis, pulmonary embolism, superficial thrombophlebitis, retinal vein occlusion, and retinal vein thrombosis with vision loss. The incidence was higher in patients with Ph+ ALL (9% of 32 patients) and BP-CML (10% of 62 patients). One of 94 patients in OPTIC experienced a VTE (Grade 1 retinal vein occlusion). Monitor for evidence of VTEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity.

Heart Failure: Fatal, serious or severe heart failure events have occurred in patients who received ICLUSIG. In PACE, heart failure occurred in 9% of 449 patients; 7% experienced serious or severe (Grade 3 or higher). Heart failure occurred in 12% of 94 patients in OPTIC; 1.1% experienced serious or severe (Grade 3 or 4). In PACE, the most frequently reported heart failure events (≥2%) were congestive cardiac failure (3.1%), decreased ejection fraction (2.9%), and cardiac failure (2%). In OPTIC, the most frequently reported heart failure events (>1 patient each) were left ventricular hypertrophy (2.1%) and BNP increased (2.1%). Monitor patients for signs or symptoms consistent with heart failure and manage heart failure as clinically indicated. Interrupt, then resume at reduced dose or discontinue ICLUSIG for new or worsening heart failure.

Hepatotoxicity: ICLUSIG can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in 3 patients, with hepatic failure occurring within 1 week of starting ICLUSIG in one of these patients. These fatal cases occurred in patients with BP-CML or Ph+ ALL. Hepatotoxicity occurred in 25% of 94 patients in OPTIC and 32% of 449 patients in PACE. Grade 3 or 4 hepatotoxicity occurred in OPTIC (6% of 94 patients) and PACE (13% of 449 patients). The most frequent hepatotoxic events were elevations of ALT, AST, GGT, bilirubin, and alkaline phosphatase. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, then resume at a reduced dose or discontinue ICLUSIG based on recurrence/severity.

Hypertension: Serious or severe hypertension, including hypertensive crisis, has occurred in patients who received ICLUSIG. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. Monitor blood pressure at baseline and as clinically indicated and manage hypertension as clinically indicated. Interrupt, dose reduce, or stop ICLUSIG if hypertension is not medically controlled. For significant worsening, labile or treatment-resistant hypertension, interrupt ICLUSIG and consider evaluating for renal artery stenosis.

Pancreatitis: Serious or severe pancreatitis has occurred in patients who received ICLUSIG. Elevations of lipase and amylase also occurred. In the majority of cases that led to dose modification or treatment discontinuation, pancreatitis resolved within 2 weeks. Monitor serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on severity. Evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms.

Increased Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective randomized clinical trial in the first line treatment of newly diagnosed patients with CP-CML, single agent ICLUSIG 45 mg once daily increased the risk of serious adverse reactions 2-fold compared to single agent imatinib 400 mg once daily. The median exposure to treatment was less than 6 months. The trial was halted for safety. Arterial and venous thrombosis and occlusions occurred at least twice as frequently in the ICLUSIG arm compared to the imatinib arm. Compared to imatinib-treated patients, ICLUSIG-treated patients exhibited a greater incidence of myelosuppression, pancreatitis, hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous tissue disorders. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

Neuropathy: Peripheral and cranial neuropathy occurred in patients in OPTIC and PACE. Some of these events in PACE were Grade 3 or 4. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Ocular Toxicity: Serious or severe ocular toxicity leading to blindness or blurred vision have occurred in ICLUSIG-treated patients. The most frequent ocular toxicities occurring in OPTIC and PACE were dry eye, blurred vision, and eye pain. Retinal toxicities included age-related macular degeneration, macular edema, retinal vein occlusion, retinal hemorrhage, and vitreous floaters. Conduct comprehensive eye exams at baseline and periodically during treatment.

Hemorrhage: Fatal and serious hemorrhage events have occurred in patients who received ICLUSIG. Fatal hemorrhages occurred in PACE and serious hemorrhages occurred in OPTIC and PACE. The incidence of serious bleeding events was higher in patients with AP-CML, BP-CML, and Ph+ ALL. Gastrointestinal hemorrhage and subdural hematoma were the most frequently reported serious hemorrhages. Events often occurred in patients with Grade 4 thrombocytopenia. Monitor for hemorrhage and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Fluid Retention: Fatal and serious fluid retention events have occurred in patients who received ICLUSIG. In PACE, one instance of brain edema was fatal and serious events included pleural effusion, pericardial effusion, and angioedema. Monitor for fluid retention and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Cardiac Arrhythmias: Cardiac arrhythmias, including ventricular and atrial arrhythmias, occurred in patients in OPTIC and PACE. For some patients, events were serious or severe (Grade 3 or 4) and led to hospitalization. Monitor for signs and symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations or dizziness) and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Myelosuppression: Grade 3 or 4 events of neutropenia, thrombocytopenia, and anemia occurred in patients in OPTIC and PACE. The incidence of myelosuppression was greater in patients with AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated. If ANC less than 1 x 109/L or platelets less than 50 x 109/L, interrupt ICLUSIG until ANC at least 1.5 x 109/L and platelets at least 75 x 109/L, then resume at same or reduced dose.

Tumor Lysis Syndrome (TLS): Serious TLS was reported in ICLUSIG-treated patients in OPTIC and PACE. Ensure adequate hydration and treat high uric acid levels prior to initiating ICLUSIG.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS (also known as Posterior Reversible Encephalopathy Syndrome) has been reported in patients who received ICLUSIG. Along with neurological signs and symptoms, hypertension may be present. Diagnosis is made with supportive findings on magnetic resonance imaging (MRI) of the brain. Interrupt ICLUSIG until resolution. The safety of resumption of ICLUSIG in patients upon resolution of RPLS is unknown.

Impaired Wound Healing and Gastrointestinal Perforation: Impaired wound healing occurred in patients receiving ICLUSIG. Withhold ICLUSIG for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of ICLUSIG after resolution of wound healing complications has not been established. Gastrointestinal perforation or fistula occurred in patients receiving ICLUSIG. Permanently discontinue in patients with gastrointestinal perforation.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal studies, ICLUSIG can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, adverse developmental effects occurred at exposures lower than human exposures at the recommended human dose. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ICLUSIG and for 3 weeks after the last dose.

ADVERSE REACTIONS

The most common (>20%) adverse reactions are rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction and AOEs. The most common Grade 3 or 4 laboratory abnormalities (>20%) are platelet count decreased, neutrophil cell count decreased, and white blood cell decreased.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceutical Co. Ltd. At 1-844-817-6468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid coadministration or reduce ICLUSIG dose if coadministration cannot be avoided.

Strong CYP3A Inducers: Avoid coadministration.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential: Verify pregnancy status of females of reproductive potential prior to initiating ICLUSIG.

Ponatinib may impair fertility in females, and it is not known if these effects are reversible.

Lactation: Advise women not to breastfeed during treatment with ICLUSIG and for 6 days following last dose.

For more information about ICLUSIG, visit www.ICLUSIG.com. For the Prescribing Information including the Boxed Warning for arterial occlusion, venous thromboembolism, heart failure, and hepatoxicity, please visit View Source For more information about ongoing research, please visit www.clinicaltrials.gov.

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

On May 19, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it will present new research data for its three lead DXd antibody drug conjugates (ADCs) in multiple types of cancer at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO21) Virtual Scientific Program to be held June 4 to 8, 2021 (Press release, Daiichi Sankyo, MAY 19, 2021, https://www.businesswire.com/news/home/20210519005576/en/Daiichi-Sankyo-Advances-Science-Across-Three-Lead-DXd-ADCs-with-New-Data-in-Multiple-Cancers-at-2021-ASCO-Virtual-Meeting [SID1234580306]).

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Presentations will highlight the company’s growing leadership in developing multiple potential treatment approaches for cancer including an oral presentation featuring extended follow-up data from a phase 1 trial of patritumab deruxtecan (HER3-DXd) in patients with locally advanced or metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer (NSCLC). Preliminary data from this trial informed the recently initiated pivotal HERTHENA-Lung01 phase 2 trial. Additionally, a dose analysis from the NSCLC cohort of the TROPION-PanTumor01 trial, which formed the basis of the datopotamab deruxtecan (Dato-DXd) dose being evaluated in the pivotal TROPION-Lung01 phase 3 trial, will be presented.

Final overall survival results from the pivotal DESTINY-Gastric01 phase 2 trial and final results from the DESTINY-CRC01 phase 2 trial of ENHERTU (trastuzumab deruxtecan) also will be featured. ENHERTU was recently highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both DESTINY-Gastric01 and DESTINY-CRC01.

"The data being presented at ASCO (Free ASCO Whitepaper) showcase Daiichi Sankyo’s sustained progress in advancing our three lead DXd ADCs across multiple cancers including lung, breast, gastric and colorectal cancers," said Ken Takeshita, MD, Global Head, Research and Development, Daiichi Sankyo. "All of these new data, biomarker research and trial-in-progress updates demonstrate our commitment to translating our innovative science and technology into potential treatment options for patients with cancer."

Additional ENHERTU data to be highlighted at ASCO (Free ASCO Whitepaper) includes updated subgroup analysis of the pivotal DESTINY-Breast01 trial in patients with metastatic HER2 positive breast cancer and brain metastases, initial results from the ENHERTU arm of the BEGONIA phase 1b/2 durvalumab combination trial in patients with triple negative breast cancer (TNBC), and pooled subgroup analysis across two phase 1 studies of patients with HER2 expressing salivary gland cancer.

Daiichi Sankyo will hold two ASCO (Free ASCO Whitepaper) conference calls for investors and analysts on Monday, June 7, 2021 from 6:30 PM-8:00 PM EDT (investors located in Japan) and on Tuesday, June 8, 2021 from 7:00 AM-8:30 AM EDT (investors located outside of Japan). Company executives will provide an overview of the ASCO (Free ASCO Whitepaper) research data, updates for the oncology portfolio and address questions from investors and analysts.

Following is an overview of the research data from the oncology portfolio of Daiichi Sankyo to be presented at ASCO (Free ASCO Whitepaper) 2021:

Presentation Title

Author

Abstract

Presentation Details

Patritumab deruxtecan (HER3-DXd)

NSCLC

Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor–resistant, EGFR-mutated non-small cell lung cancer (NSCLC)

P. Jänne

9007

Oral Presentation

Lung Cancer – Non-Small Cell Metastatic: Friday, June 4, 2021; 1:00 – 4:00 PM EDT

A randomized phase 2 study of patritumab deruxtecan (U3-1402) in patients with previously treated metastatic or locally advanced EGFR-mutated NSCLC

P. Jänne

TPS9139

Poster Presentation

Datopotamab deruxtecan (Dato-DXd)

NSCLC

TROPION-PanTumor01: dose analysis of the TROP2 directed antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd; DS-1062) for the treatment of advanced or metastatic non-small cell lung cancer

F. Meric-Bernstam

9058

Poster Presentation

A randomized, phase 3 study of datopotamab deruxtecan (Dato-DXd; DS-1062) vs docetaxel in previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (TROPION-Lung01)

K. Yoh

TPS9127

Poster Presentation

Breast

BEGONIA: phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): addition of Arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062)

P. Schmid

TPS1105

Poster Presentation

ENHERTU (trastuzumab deruxtecan; T-DXd)

Colorectal

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2 expressing metastatic colorectal cancer (mCRC): final results from a phase 2, multicenter, open-label study (DESTINY-CRC01)

T. Yoshino

3505

Oral Presentation

Gastrointestinal Cancer – Colorecal and Anal: Monday, June 7; 1:15 – 4:15 PM EDT

Trastuzumab deruxtecan in patients with HER2 overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC): a randomized, multicenter, phase 2 study (DESTINY-CRC02)

K. Raghav

TPS3620

Poster Presentation

Gastric

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2 positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01)

K. Yamaguchi

4048

Poster Presentation

Quality-adjusted time without symptoms or toxicity (Q-TWiST) of trastuzumab deruxtecan (T-DXd) versus chemotherapy in patients with advanced gastric cancer from the DESTINY-Gastric01trial

D. Cella

4057

Poster Presentation

Breast

Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: a subgroup analysis of the DESTINY-Breast01 trial

G. Jerusalem

526

Poster Presentation

BEGONIA: phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple negative breast cancer (TNBC): Initial results from Arm 1, D+paclitaxel (P), and Arm 6, D+trastuzumab deruxtecan

P. Schmid

1023

Poster Discussion Session

Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2 positive advanced or metastatic breast cancer: a phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07)

F. Andre

TPS1096

Poster Presentation

Prevalence of HER2 low in breast cancer subtypes using the VENTANA anti-HER2/neu (4B5) assay

M. Scott

1021

Poster Discussion Session

Machine learning models to quantify HER2 for real-time tissue image analysis in prospective clinical trials

B.Glass

3061

Poster Presentation

Pan Tumor

Trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing salivary duct carcinoma: Subgroup analysis of two phase 1 studies

H. Bando

6079

Poster Presentation

A phase 2, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of solid tumors harboring specific HER2 activating mutations (DESTINY-PanTumor01)

B.Li

TPS3162

Poster Presentation

About the DXd ADC Portfolio of Daiichi Sankyo

The DXd ADC portfolio of Daiichi Sankyo currently consists of seven ADCs with six in clinical development across multiple types of cancer. The company’s three lead ADCs include ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca; and patritumab deruxtecan (HER3-DXd), a HER3 directed ADC. Three additional ADCs including DS-7300 (B7-H3), DS-6157 (GPR20) and DS-6000 (CDH6) are being developed through a strategic research collaboration with Sarah Cannon Research Institute.

Each ADC is designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen. Each ADC consists of a monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved under accelerated approval in the U.S, under conditional marketing authorization in the EU and the UK, and under the conditional early approval system in Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

Patritumab deruxtecan, datopotamab deruxtecan, DS-7300, DS-6157 and DS-6000 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

U.S. Important Safety Information for ENHERTU

Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

Adverse Reactions
Metastatic Breast Cancer
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

Locally Advanced or Metastatic Gastric Cancer
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY‑Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

On May 19, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company, reported that 16 abstracts representing the breadth of the Gilead-Kite Oncology portfolio will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 4-8, 2021 (Press release, Gilead Sciences, MAY 19, 2021, View Source [SID1234580305]). The abstracts, including two oral presentations, expand on the clinical profiles of Gilead’s antibody-drug conjugate (ADC), as well as Kite’s chimeric antigen receptor (CAR) T-cell therapies across a range of cancers, including in existing indications and for investigational uses.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"Gilead-Kite Oncology is rapidly advancing transformative science for people facing historically difficult-to-treat cancers," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Our first-in-class, TROP-2 directed ADC therapy is already having a meaningful impact for people with metastatic triple-negative breast and urothelial cancers, and data at ASCO (Free ASCO Whitepaper) will add further insight into its utility in TNBC in both monotherapy and future combination treatment approaches."

"CAR T-cell therapy has changed the lives of patients suffering from certain forms of non-Hodgkin lymphoma, and our data at ASCO (Free ASCO Whitepaper) demonstrate important progress in extending the benefits to more patients in need," said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. "As we aim to bring CAR T to people with many different hematologic malignancies, we are just beginning to scratch the surface of what is possible."

A list of accepted abstracts follows here:

Abstract Disposition

Abstract Title

Gilead Presentations

Oral #1011

6:00 am PT/9:00 am ET

Outcomes in Patients Aged ≥65 Years in the Phase 3 ASCENT Study of Sacituzumab Govitecan (SG) in Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #1077

Assessment of Sacituzumab Govitecan (SG) versus Treatment of Physician’s Choice (TPC) Cohort by Agent in the Phase 3 ASCENT Study of Patients with Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #1080

Assessment of Sacituzumab Govitecan (SG) in Patients with Prior Neoadjuvant/Adjuvant Chemotherapy in the Phase 3 ASCENT Study in Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #TPS602

Phase 3 Postneoadjuvant Study Evaluating Sacituzumab Govitecan, an Antibody Drug Conjugate in Primary HER2-Negative Breast Cancer Patients with High Relapse Risk After Standard Neoadjuvant Treatment – SASCIA

Poster #TPS1102

Saci-IO HR+: Randomized Phase 2 Trial of Sacituzumab Govitecan (SG) +/- Pembrolizumab in PD-L1+ Hormone Receptor-Positive (HR+) / HER2- Metastatic Breast Cancer (MBC)

Poster #TPS1106

Saci-IO TNBC: Randomized Phase 2 Trial of Sacituzumab Govitecan (SG) +/- Pembrolizumab in PD-L1– Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #TPS7055

Magrolimab + Azacitidine versus Azacitidine + Placebo in Untreated Higher Risk Myelodysplastic Syndrome (MDS): The Phase 3, Randomized, ENHANCE Study

Poster #2559

GS-3583, a Novel FLT3 Agonist Fc Fusion Protein, to Expand Conventional Dendritic Cells in Healthy Volunteers

Poster #TPS3147

Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS-3583, a FLT3 Agonist Fc Fusion Protein, in Patients with Advanced Solid Tumors

Kite Presentations

Oral #7002

11:30 am PT/2:30 pm ET

Phase 2 Results of the ZUMA-3 Study Evaluating KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL)

Poster #7515

Outcomes in ZUMA-5 with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL) Who Had the High-Risk Feature of Progression within 24 Months from Initiation of First Anti-CD20–Containing Chemoimmunotherapy (POD24)

Poster #7536

Favorable Tumor Immune Microenvironment (TME) and Robust Chimeric Antigen Receptor (CAR) T-Cell Expansion May Overcome Tumor Burden and Promote Durable Efficacy with Axicabtagene Ciloleucel (Axi-Cel) in Large B Cell Lymphoma (LBCL)

Poster #7547

Outcomes with KTE-X19 in Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL) in ZUMA-2 Who Had Progression of Disease within 24 Months of Diagnosis (POD24)

Poster #7548

Updated Outcomes with Axicabtagene Ciloleucel (Axi-Cel) Retreatment in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL) in ZUMA-5

Poster #7552

Real-World Evidence of Axicabtagene Ciloleucel (Axi-Cel) for the Treatment of Large B-Cell Lymphoma (LBCL) in the United States

Poster #e19548

Online Publication Only

Clinical Outcomes in Patients Relapsed/Refractory After ≥ 2 Prior Lines of Therapy for Follicular Lymphoma: A Systematic Literature Review and Meta-Analysis

All poster presentations will be made available on-demand beginning Friday, June 4 at 6:00 am PT/9:00 am ET.

For more information, including a complete list of abstract titles at the meeting, please visit: View Source