On June 3, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported the presentation of three posters at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL today and online (Press release, Rigel, JUN 3, 2024, View Source [SID1234644024]). Presentations include five-year results from the pivotal cohort of the registrational Phase 2 trial of REZLIDHIA (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML), the safety and efficacy of olutasidenib treatment in a subgroup analyses of elderly patients with R/R mIDH1 AML, and an overview of the ongoing Phase 1b trial of R2891, a potent and selective inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS).

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"Our presentations at ASCO (Free ASCO Whitepaper) build on the strength of REZLIDHIA’s data, reinforcing its important role in the R/R mIDH1 AML treatment landscape. REZLIDHIA continues to demonstrate durable responses and was well tolerated, even in difficult to treat and elderly patients with mIDH1 AML who have more safety concerns," said Raul Rodriguez, Rigel’s president and CEO. "In addition, we are sharing an overview of the ongoing Phase 1b trial of R289 in lower-risk MDS, an area of high unmet need. We believe R289 could potentially provide a new treatment option to patients who have failed other agents."

Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: 6528
Title: Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results from the Phase 2 Pivotal Cohort
Presenter: Jorge E. Cortes, M.D.
Location: McCormick Place South, Exhibit Hall A

An additional two years of data, beyond the results that led to FDA approval of olutasidenib, further demonstrates the durable responses observed with olutasidenib in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. The safety profile was consistent with what was previously reported.
Of 147 efficacy evaluable patients, complete remission (CR) or CR with partial hematologic recovery (CRh) was achieved in 35%. The median time to CR/CRh was 1.9 months and median duration of CR/CRh was 25.3 months, with maximum duration ongoing at 54.6 months. Overall response rate was 48%, with median duration 15.5 months and maximum duration ongoing at 54.6 months. Median overall survival was 11.6 months.
Transfusion independence (for ≥56 days) from red blood cells was achieved in 34 patients (39%) who were dependent at baseline and from platelets was achieved in 28 patients (41%) who were dependent at baseline.
In the 12 patients that were R/R to prior venetoclax, 33% achieved a CR/CRh; median duration of CR/CRh was not reached (ongoing at 50.6 months), and median overall survival was 16.2 months.
Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: 6527
Title: Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.
Location: McCormick Place South, Exhibit Hall A

Olutasidenib was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions, consistent with the population in the pivotal cohort of the Phase 2 registrational trial. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with olutasidenib.
In this subgroup analyses of the registrational Phase 2 trial of olutasidenib in 45 participants aged 75 and older with R/R mIDH1 AML, 31% of patients achieved CR/CRh; median time to CR/CRh was 1.5 months, and median duration of CR/CRh was 25.9 months.
Of the five elderly patients who were R/R to prior venetoclax, four patients (80%) achieved an overall response, including two patients (40%) with CR/CRh.
Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: TPS6591
Title: Phase 1b Trial of IRAK 1/4 Inhibition for Lower-Risk Myelodysplastic Syndrome Refractory/Resistant to Prior Therapies: A Trial in Progress
Presenter: Guillermo Garcia-Manero, M.D.
Location: McCormick Place South, Exhibit Hall A

An overview of the study design of the ongoing Phase 1b trial evaluating R289 in patients with LR-MDS will be presented. The primary endpoint for this trial is safety with key secondary endpoints including preliminary efficacy and evaluation of pharmacokinetic properties.
Enrollment in dose levels 1 (250 mg QD), 2 (500 mg QD), and 3 (750 mg QD) has been completed. Two additional dose levels with twice daily dosing have been added (250 mg BID and 500/250 mg) and the trial is actively recruiting.
To learn more about Rigel and the company’s clinical and commercial hematology and oncology portfolio, visit Booth #11059 during ASCO (Free ASCO Whitepaper).

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.5

About REZLIDHIA
INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

On June 3, 2024 Johnson & Johnson reported new data from the Phase 2 PALOMA-2 study evaluating subcutaneous (SC) amivantamab combined with lazertinib as a first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) or L858R mutations (Press release, Johnson & Johnson, JUN 3, 2024, View Source [SID1234644040]). These data, which were featured in a late-breaking poster presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #LBA8612), showed a comparable response rate in patients treated with SC amivantamab and lazertinib compared to those treated with the intravenous (IV) formulation in the MARIPOSA study, which established the combination of amivantamab and lazertinib as superior to osimertinib. SC amivantamab was associated with significantly lower rates of infusion-related reactions (IRRs) and shorter treatment time compared with the IV formulation.1

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"These encouraging data show similar response rates in patients treated with the subcutaneous administration of amivantamab compared with the IV formulation," said Professor Nicolas Girard, Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, France, and study author.* "With favorable tolerability based on fewer infusion-related reactions, this formulation has the potential to address a current unmet need in the treatment of EGFR-mutant lung cancer."

In the PALOMA-2 study, Cohorts 1 and 6 enrolled patients with treatment-naïve, EGFR ex19del or L858R-mutated advanced NSCLC, a patient population similar to the MARIPOSA study population. In Cohort 1 prophylactic anticoagulation use was recommended, and in Cohort 6 it was required. As of January 6, 2024, 68 and 58 patients were enrolled in Cohorts 1 and 6, respectively. At a median follow-up of 8.6 months, across all patients, SC amivantamab combined with lazertinib demonstrated an overall response rate (ORR) of 77 percent (95 percent Confidence Interval [CI], 68-84) as assessed by the investigator per RECIST v1.1.** (primary endpoint) and 79 percent (95 percent CI, 70-86) as assessed by blinded independent central review. A similar ORR of 86 percent (95 percent CI, 83-89) was observed with IV amivantamab in combination with lazertinib, as determined by a blinded independent central review in the Phase 3 MARIPOSA study. Average administration time was approximately five minutes versus the IV administration of 2-4 hours. Median duration of response was not estimable in both cohorts.1

The pooled analysis from Cohort 1 and Cohort 6 showed the safety profile for SC amivantamab was consistent with previous reports, with no new safety signals identified. The most common treatment-emergent adverse events (AEs) (≥ 20 percent) across all patients were paronychia (71 percent), rash (61 percent) and hypoalbuminemia (48 percent). IRRs were reported in 15 percent of patients across the two cohorts. Discontinuation of all medicines due to treatment-related AEs occurred in approximately nine percent of all patients. Prophylactic anticoagulation was administered to 71 percent of patients in Cohort 1 and 100 percent of those in Cohort 6. Venous thromboembolic events (VTEs) were reported in 18 and seven percent of patients in Cohorts 1 and 6, respectively, with no dose reductions or discontinuations reported due to VTEs. These findings suggest prophylactic anticoagulation can be safely implemented and reduce the incidence of VTEs with the combination of amivantamab plus lazertinib.1

"The safety and tolerability data from the PALOMA-2 study highlight the potential of subcutaneous amivantamab as an important therapy in the first-line treatment of patients with EGFR-mutant lung cancer," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "As we advance our robust pipeline and portfolio for patients with lung cancer, we remain dedicated to developing safe and effective therapies that offer distinct benefits in the treatment of this disease."

About the PALOMA-2 Study

PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and pharmacokinetics (PK) of first-line SC amivantamab (administered via manual injection) combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. Sixty-eight and 58 patients were enrolled in Cohorts 1 and 6, respectively. Prophylactic anticoagulation for the first four months of treatment was recommended in Cohort 1 and mandatory in Cohort 6. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1.2

About RYBREVANT

RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.3 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

RYBREVANT is also approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT for this indication.

In December 2023, Johnson & Johnson submitted a supplmental Biologics License Application (sBLA) together with a New Drug Application (NDA) to the U.S. FDA for RYBREVANT in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. This submission is based on the Phase 3 MARIPOSA study and was granted Priority Review in February 2024. A marketing authorization application (MAA) and type II extension of indication application were also submitted to the EMA seeking approval of lazertinib in combination with RYBREVANT based on the MARIPOSA study.

In November 2023, Johnson & Johnson submitted an sBLA to the U.S. FDA for RYBREVANT in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT for this indication.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

Amivantamab-vmjw (RYBREVANT) plus carboplatin and pemetrexed as a preferred (Category 1 recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.4 †‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a preferred (Category 1 recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.4 †‡
Amivantamab-vmjw (RYBREVANT) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.4 †‡
RYBREVANT is being studied in multiple clinical trials in NSCLC, including:

The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.5
The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.2
The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.6
The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.7
The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.8
The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.9
The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in patients with advanced NSCLC.10
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.11
The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC.12
The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.13
The Phase 2 SKIPPirr (NCT05663866) study exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.14
For more information, visit: View Source

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.17,18,19,20,21,22 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.23 The five year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.24,25 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.26 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.27

RYBREVANT IMPORTANT SAFETY INFORMATION3

WARNINGS AND PRECAUTIONS

The safety population of RYBREVANT with carboplatin and pemetrexed described in Warnings and Precautions was based on 151 patients in the PAPILLON study.

The safety population of RYBREVANT as a single agent described in Warnings and Precautions was based on 129 patients in the CHRYSALIS study.

Infusion-Related Reactions

RYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting.

RYBREVANT with Carboplatin and Pemetrexed

RYBREVANT in combination with carboplatin and pemetrexed can cause infusion-related reactions. Based on the safety population, infusion-related reactions occurred in 42% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (1.3%) adverse reactions. The incidence of infusion modifications due to IRR was 40%, and 0.7% of patients permanently discontinued RYBREVANT.

RYBREVANT as a Single Agent

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62%, and 1.3% of patients permanently discontinued RYBREVANT due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids, and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity.

Interstitial Lung Disease/Pneumonitis

RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis.

RYBREVANT with Carboplatin and Pemetrexed

Based on the safety population, Grade 3 ILD/pneumonitis occurred in 2.6% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed. All patients required permanent discontinuation.

RYBREVANT as a Single Agent

Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions

RYBREVANT can cause rash (including dermatitis acneiform), pruritus, and dry skin.

RYBREVANT with Carboplatin and Pemetrexed

RYBREVANT in combination with carboplatin and pemetrexed can cause dermatologic adverse reactions. Based on the safety population, rash occurred in 89% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (19%) adverse reactions. Rash leading to dose reductions occurred in 19% of patients; 2% permanently discontinued RYBREVANT, and 1.3% discontinued pemetrexed.

RYBREVANT as a Single Agent

Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT as a single agent.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin.

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce, or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity

RYBREVANT can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis.

RYBREVANT with Carboplatin and Pemetrexed

Based on the safety population, RYBREVANT in combination with carboplatin and pemetrexed can cause ocular toxicity including blepharitis, dry eye, conjunctival redness, blurred vision, and eye pruritus. All events were Grade 1-2.

RYBREVANT as a Single Agent

Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce, or permanently discontinue RYBREVANT based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT.

Adverse Reactions

RYBREVANT with Carboplatin and Pemetrexed

For the 151 patients in the PAPILLON clinical trial who received RYBREVANT in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

Serious adverse reactions occurred in 37% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.

RYBREVANT as a Single Agent

For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT as a single agent, the most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Serious adverse reactions occurred in 30% of patients who received RYBREVANT. Serious adverse reactions in ≥2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.

Please read the full Prescribing Information for RYBREVANT.

On June 3, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported its research collaborators from Washington University’s Siteman Cancer Center will lead an oral presentation today at the 2024 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting highlighting the potential role of liquid biopsy in addressing racial inequities in enrollment in clinical trials and in the use of targeted therapies for advanced breast cancer (Press release, Guardant Health, JUN 3, 2024, View Source [SID1234644057]).

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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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The Rapid Oral Abstract Session (#1017), titled "Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer," will be held between 11:30 am and 1:00 pm CT in Hall D1.

The retrospective study, led by first author Emily Podany, MD, and senior author Andrew Davis, MD, both from Washington University, focused on patients with hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer with PIK3CA mutations, which had an equal incidence in Black and White patients. The 1,327 patients in the study, who were treated at Washington University in St. Louis, Massachusetts General Hospital, and Northwestern University, had the Guardant360 liquid biopsy test as part of clinical care and these results were combined with annotated clinical data. Results indicated that Black patients were significantly less likely than White patients to receive PIK3CA targeted therapy or to be enrolled in a clinical trial for biomarkers that required targetable mutations identified via circulating tumor DNA (ctDNA). There were no differences in the use of therapies that did not require a targetable mutation identified via ctDNA.

"These data show clinical inequities in the use of targeted therapies and enrollment in clinical trials, which must be the focus of future interventions," said Podany. "We must now identify ways to ensure all patients equitably receive the recommended precision medicine treatments based on the results of ctDNA testing."

"These data highlight the importance of using ctDNA to identify targetable mutations," noted Davis. "And they reinforce the urgent need to ensure equitable implementation of precision medicine therapies for patients of all races."

The study is part of an ongoing collaboration between Guardant Health and the multicenter Precision Medicine Academic Consortium (PMAC) aimed at advancing the use of liquid biopsy in patients with metastatic breast cancer.

"This landmark study highlights the importance of equitable access to precision medicine," said Craig Eagle, MD, chief medical officer of Guardant Health. "The results confirm the potential role liquid biopsy can have in helping researchers and clinicians equitably match patients with appropriate trials and clinically effective therapies."

Currently, PMAC is working with Guardant Health to validate genomic findings from this and prior projects using the GuardantINFORM clinical-genomic dataset of over 400,000 patients with advanced cancer. The collaboration will continue to pursue future research focused on increasing equitable utilization of targeted therapies.

"The current study demonstrates the importance of studying real-world annotated molecular data related to the use of ctDNA testing and targeted therapies in advanced cancer," said Massimo Cristofanilli, MD, co-founder of PMAC. "It provides valuable insights that can help us understand the complex relation among biological, ethnic and social diversity and offers potential tools to overcome inequity in care."

The full abstract for the study and a list of all abstracts being presented at the meeting can be found at the ASCO (Free ASCO Whitepaper) website.

For more information and updates from the meeting, follow Guardant Health on LinkedIn and X (Twitter) or visit ASCO (Free ASCO Whitepaper) booth #28115.

On June 3, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that management will participate in a fireside chat at the Goldman Sachs 45th Annual Global Healthcare Conference on Monday, June 10, 2024, at 1:20 p.m. ET (Press release, Alector, JUN 3, 2024, View Source [SID1234643991]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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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A live webcast of the fireside chat will be available on the "Events & Presentations" page within the Investors section of the Alector website at View Source A replay will be available on the Alector website for 90 days following the event.

On June 3, 2024 Genmab A/S (Nasdaq: GMAB) reported that data from the Phase 2 innovaTV 207 trial (NCT03485209) Part C (n=40), investigating tisotumab vedotin, an antibody-drug conjugate directed to tissue factor, demonstrated encouraging antitumor activity as a monotherapy in patients with head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on or after first-line therapy (Press release, Genmab, JUN 3, 2024, View Source [SID1234644009]). The study showed 32.5% of patients achieved a confirmed objective response rate (cORR), one patient experienced a complete response (CR) and 12 achieved a partial response (PR). These results were presented in a rapid oral session today at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, Illinois, May 31 – June 4, 2024.

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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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In the HNSCC cohort of innovaTV 207 Part C (n=40), median duration of response (DOR) was 5.6 months and median time-to-response (TTR) was 1.4 months. All patients were required to have received a platinum-based regimen in the recurrent or metastatic setting or have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor (CPI), if eligible. The study also showed that among patients with no more than one or two lines of therapy in the recurrent or metastatic setting (n=25), 40% had achieved a cORR at the time of data cut-off.

"Most patients with recurrent or metastatic head and neck squamous cell carcinoma experience disease progression despite the use of platinum-based therapy and immunotherapy, and treatment options are limited," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab, "These updated results underscore the importance of our ongoing work with our partner to advance the clinical development program for tisotumab vedotin and investigate potential treatment options for pretreated patients living with unmet needs."

The safety findings were consistent with previous tisotumab vedotin trials, and no new safety signals were observed. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 67.5% of patients, and the most common were peripheral neuropathy events (40%). Adverse events of special interest (of any grade) were prespecified for ocular, peripheral neuropathy, and bleeding events, and occurred in 52.5%, 47.5%, and 40% patients, respectively.

As of December 2023, 40 patients with recurrent or metastatic HNSCC were treated with tisotumab vedotin monotherapy (1.7 mg/kg intravenously, once every two weeks). In this cohort, 32 (80%) received prior platinum-based therapy, 19 (47.5%) received at least two prior lines of systemic therapy (median: 2; range: 1-3), 40 (100%) received prior CPI, 23 (57.5%) received prior taxane, and 27 (67.5%) received prior cetuximab. The primary sites at diagnosis were oropharynx (n=16), larynx (n=13), and oral cavity (n=9).

About the innovaTV 207 Trial
The innovaTV 207 trial (NCT03485209) is an open-label, global, Phase 2, multicohort, multicenter study evaluating tisotumab vedotin monotherapy or in combination for advanced solid tumors. In Part C, patients with recurrent or metastatic HNSCC received tisotumab vedotin monotherapy (1.7 mg/kg IV once every two weeks). All patients were required to have received a platinum-based regimen, either in the recurrent/metastatic setting, or to have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor, if eligible. The primary endpoint of the trial is confirmed objective response rate (cORR) per RECIST 1.1 per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Selected secondary endpoints include duration of response (DOR), time-to-response (TTR), and safety. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin
Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

Tisotumab vedotin (TIVDAK) has received full approval by the U.S. FDA for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Tisotumab vedotin in HNSCC is not approved in any country, including the U.S. and the EU. The safety and efficacy of tisotumab vedotin has not been established for these investigational uses.

Virtual mid- to late-stage pipeline update at ASCO (Free ASCO Whitepaper) 2024
On Monday, June 3, at 9:00 AM CDT (10:00 AM EDT/4:00 PM CEST), Genmab will host a review of data presented at ASCO (Free ASCO Whitepaper) from its mid- to late-stage pipeline. The event will be virtual and webcast live. Details, including the webcast link and registration will be available on www.genmab.com. This meeting is not an official program of the ASCO (Free ASCO Whitepaper) Annual Meeting.