On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported the presentation of additional data from the Phase 3 TIVO-3 study comparing FOTIVDA (tivozanib) to sorafenib in relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies (Press release, AVEO, MAY 19, 2021, View Source [SID1234580276]). The data, which includes updated durability of response (DOR) and overall survival (OS) results, as well as an analysis of treatment-emergent adverse events (TEAEs) across study arms, will be featured in two poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 4-8 in a virtual setting. FOTIVDA, AVEO’s oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), is approved by the U.S. Food and Drug Administration for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies.

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"With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated options in the relapsed or refractory setting," said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. "The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and these long-term follow up results continue to demonstrate the depth and durability of responses to FOTIVDA, as well as a tolerability profile that is particularly important in the later-stage treatment setting."

"FOTIVDA has demonstrated a differentiated clinical profile, and we are very pleased with initial receptivity to this differentiation and to the importance of the unique dataset that the TIVO-3 study represents in the commercial setting," said Michael Bailey, president and chief executive officer of AVEO. "We were also pleased to see efficacy advantages relative to sorafenib were maintained or improved with longer follow-up. We look forward to continuing to elucidate FOTIVDA’s potential in the clinic, particularly in the immunotherapy combination setting, with patient enrollment in the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO (nivolumab) anticipated to commence mid-year and execution of the Phase 2 hepatocellular carcinoma DEDUCTIVE trial in combination with IMFINZI (durvalumab) ongoing."

TIVO-3 ASCO (Free ASCO Whitepaper) Data

TIVO-3 is a Phase 3, open-label study that enrolled patients with metastatic RCC whose disease progressed on two or more prior systemic regimens, one of which included a VEGFR TKI. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk category (favorable, intermediate, or poor) and type of prior therapy (two prior VEGFR TKIs, VEGFR TKI plus checkpoint inhibitor, VEGFR TKI plus any other systemic agent) then randomized 1:1 to receive tivozanib or sorafenib. Results from the study were published in Lancet Oncology (December 2019). Additional analyses and long-term follow up results from the TIVO-3 study to be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting include:

Durability of Response and Updated Overall Survival. Tivozanib demonstrated clinically meaningful and statistically significant improvements in overall response rate (ORR) and DOR compared to sorafenib in 350 patients randomized 1:1 with highly relapsed or refractory RCC. As of a January 15, 2021 data cutoff date, the median DOR for patients treated with tivozanib was 20.3 months (95% CI, 9.8-29.9 months) compared to 9.0 months (95% CI, 3.7-16.6 months) for patients treated with sorafenib. The ORR for patients treated with tivozanib was 23% compared to 11% for patients treated with sorafenib. Furthermore, long-term OS relative to sorafenib continues to improve (hazard ratio (HR): 0.91 [95% CI, 0.716-1.165; p=0.47]). The OS HR assesses the relative risk of death for the entirety of the data set.
Temporal Characteristics of Treatment-Emergent Adverse Events and Dose Modifications. Patients in the TIVO-3 study had longer duration of treatment exposure with tivozanib than sorafenib (11.9 cycles vs. 6.7 cycles), but fewer all-grade and grade ≥3 TEAEs. TEAEs were generally similar with tivozanib and sorafenib. Time to dose modifications was longer with tivozanib than sorafenib. Among those with the same TEAEs, dose reductions, interruptions, or discontinuations were required more frequently with sorafenib than tivozanib.
A copy of each poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC).
Abstract: 4546
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
Title: Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the Phase 3 TIVO-3 study of relapsed or refractory mRCC.
Abstract: 4567
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On May 19, 2021 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company’s management will participate in Cowen’s 2nd Annual Virtual Oncology Innovation Summit (Press release, MacroGenics, MAY 19, 2021, View Source [SID1234580292]). MacroGenics’ management will participate in a fireside chat with the analyst on Thursday, May 20, 2021, at 9:20 am ET.

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A webcast of the fireside chat may be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source The Company maintains archived replays of webcasts on its website for 30 days after each conference.

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 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported that an abstract detailing clinical data from its U.S. phase 1 study of uliledlimab in combination with atezolizumab (TECENTRIQ) in patients with advanced cancer will be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8, 2021 (Press release, I-Mab Biopharma, MAY 19, 2021, View Source [SID1234580324]). The abstract has been selected as one of the Top 12 abstracts for poster discussion during the Developmental Therapeutics – Immunotherapy session.

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Uliledlimab is a humanized CD73 antibody and is designed to counter the adenosine-mediated immunosuppressive tumor microenvironment, rendering anti-tumor immune cells to act more effectively in response to checkpoint immunotherapies. Preclinical studies have shown that when combined with a PD-(L)1 antibody, uliledlimab exhibited a superior and synergistic inhibitory effect on tumor growth versus PD-(L)1 mono-therapy. Uliledlimab is a highly differentiated CD73 antibody that binds to a unique epitope of CD73 to confer pharmacological advantages by avoiding the "hook effect" commonly seen with other CD73 antibodies.

The U.S. phase 1 dose escalation study of uliledlimab in combination with atezolizumab showed that the treatment is safe and well tolerated with no dose-limiting toxicity. All treatment related adverse events were either grade 1 or grade 2. Uliledlimab demonstrated a linear pharmacokinetic (PK) profile and reached full receptor occupancy on B cells at the middle and high dose levels with no "hook effect." Patients who participated in the study had advanced cancers and exhausted other cancer therapies. Among the 13 efficacy-evaluable patients dosed at ≥ 10 mg/kg, three patients had complete or partial responses (objective response rate = 23%) and three had stable disease (disease control rate = 46%). The clinical activity was observed in both PD-(L)1 treatment naïve and refractory cancer patients, including one partial response patient who previously failed nivolumab. Tumor types of patients who had complete or partial responses or stable disease included ovarian clear cell carcinoma, non-small cell lung cancer and a few other cancers. The three responders were identified as the only patients who exhibited higher co-expression of tumor CD73 and PD-L1 as compared to non-responders, indicating a correlation between higher CD73 expression and clinical activity of uliledlimab and a potential role of CD73 as a predictive biomarker to warrant further investigation.

Details of the poster discussion session are as follows:

Abstract No.

2511

Poster Title

Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer

Poster Discussion Session

Developmental Therapeutics – Immunotherapy

Presentation Date and Time

June 4, 2021, 9:00 AM (ET)

Presenting Author

Dr. Francisco Robert, Professor of Medicine, University of Alabama-Birmingham

"Despite recent breakthroughs with PD-1/PD-L1 therapies, clinical non-response rates to such treatments remain high in cancer patients. Uliledlimab, through its unique mechanism of action, has shown its promise to address this unmet medical need by breaking tumor resistance to immunotherapies through combination therapy," said Dr. Joan Shen, CEO of I-Mab. "The results from this phase 1 study are very encouraging in terms of potential therapeutic role of uliledlimab to treat multiple cancers, especially in patients who do not respond to PD-1/PD-L1 therapies. The differentiated properties of uliledlimab may provide additional pharmacological and treatment advantages, and we look forward to advancing the development of uliledlimab both globally and in China."

In parallel development, I-Mab has made significant progress in clinical trials in China to evaluate uliledlimab in combination with toripalimab (TUOYI) in patients with advanced or metastatic cancers, including non-small cell lung cancer, who are refractory to or intolerant of available therapies.

I-Mab will host an investor call on June 7, 2021 to discuss the clinical data presented at the conference. Details of conference call and webcast information will be provided subsequently.

About Uliledlimab (TJD5)

Uliledlimab (TJD5) is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine in turn binds to adenosine receptors on relevant immune cells and inhibits anti-tumor immune responses in tumor microenvironment. Uliledlimab is expected to offer clinical benefit by suppressing tumor growth in concert with checkpoint therapies such as PD-(L)1 antibodies. Uliledlimab is effective in anti-tumor activities through a unique intra-dimer binding, leading to differentiated and favorable functional properties as evident in preclinical studies.

On May 19, 2021 EXACT THERAPEUTICS AS ("EXACT-Tx" or the "Company"), a clinical stage precision medicine company utilizing Acoustic Cluster Therapy (ACT) across multiple therapeutic areas, reported that it has been granted a patent for its innovative Acoustic Cluster Therapy technology in Japan (Press release, Exact Therapeutics, MAY 19, 2021, View Source [SID1234580357]).

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The patent covers EXACT-Tx`s unique microbubble/microdroplet formulation and its use, co-administered with a range of pharmaceutical agents for ultrasound mediated therapeutic targeting.

"We are delighted with the decision of the Japanese Patent Office in granting this important patent for ACT, which complements the existing patent granted in China in November 2019. This core patent represents the foundation of our dynamic IP strategy, which encompasses the use of ACT with a variety of therapeutics across a multitude of indications",

said Dr Rafiq Hasan, CEO of EXACT Therapeutics AS.