RYBREVANT® and Lazertinib Combination for Patients with Non-Small Cell Lung Cancer and EGFR Mutations

Presentations at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) Span Relapsed/Refractory Disease and Frontline Treatment in Patients with EGFR-Positive Non-Small Cell Lung Cancer

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data from the Phase 1b/2 CHRYSALIS-2 study (NCT04077463) cohort evaluating the safety and tolerability of the combination of RYBREVANT® (amivantamab-vmjw) with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) lazertinib and platinum-based chemotherapy (carboplatin and pemetrexed) in patients with relapsed/refractory non-small cell lung cancer (NSCLC) and EGFR mutations.[1] These findings and additional updates, including data on RYBREVANT® in combination with lazertinib in the frontline setting for patients with NSCLC will be presented at the IASLC 2022 WCLC hosted by the IASLC August 6-9 in Vienna, Austria.

CHRYSALIS-2 (NCT04077463) is an ongoing clinical trial evaluating RYBREVANT® in combination with lazertinib in patients with advanced NSCLC with EGFR exon 19 deletion mutations or L858R activating mutations.[2] One cohort of CHRYSALIS-2 evaluates the combination of RYBREVANT® and lazertinib with carboplatin and pemetrexed.[1] Results from the RYBREVANT®, lazertinib, carboplatin and pemetrexed combination cohort (n=20) will be featured in a mini oral presentation (Abstract #MA07.04) at the IASLC 2022 WCLC.[1] Enrolled participants received a median of two prior lines of therapy.[1] Prior therapies included osimertinib (n=14), gefitinib (n=3), afatinib (n=3), and platinum-based chemotherapy (n=5), among others.[1]

After a median follow-up of 7.1 months, the combination of RYBREVANT® and lazertinib with carboplatin and pemetrexed yielded an overall response rate (ORR) of 50 percent (95 percent confidence interval [CI];27-73), with 15 out of 20 patients remaining on treatment.[1] The observed safety profile of this treatment combination was consistent with the previously reported safety profile of each individual agent; no evidence of new safety signals or additional toxicity was observed.[1] The most common treatment-emergent adverse events (AEs) included neutropenia (85 percent), rash (75 percent), infusion-related reaction and stomatitis (60 percent), fatigue and paronychia (50 percent each), and thrombocytopenia and nausea (40 percent each).[1]

RYBREVANT® (amivantamab-vmjw) received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 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.[8] This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT® has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer* prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option with a 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.[9]†^

RYBREVANT® is being studied in multiple clinical trials, including for untreated advanced EGFR-mutated NSCLC in the Phase 3 MARIPOSA (NCT04487080NCT04487080) study assessing RYBREVANT® in combination with lazertinib as an alternative to osimertinib for frontline treatment; the Phase 3 MARIPOSA-2 (NCT04988295) study to evaluate the combination of RYBREVANT® and lazertinib with platinum-based chemotherapy in patients with EGFR-mutated NSCLC after disease progression on or after osimertinib; the Phase 1/1b CHRYSALIS-2 (NCT04077463) study assessing the combination of RYBREVANT® and lazertinib in patients who have progressed after treatment with osimertinib and chemotherapy; the Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations.

About Lazertinib
Lazertinib is an oral, third-generation, brain-penetrant, EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR.[12] Interim safety and efficacy results from the lazertinib Phase 1/2 study were published in The Lancet Oncology in 2019. In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, and NSCLC makes up 80 to 85 percent of all lung cancers.[13],[14] The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.[15] Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.16 EGFR mutations are present in 10 to 15 percent[15],[16][17],[18],[19] of people with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asians.[20],[21] The five-year survival rate for all people with metastatic NSCLC and EGFR mutations treated with EGFR TKIs is less than 20

Ocular Toxicity[8]
RYBREVANT® can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. 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[8]
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 final dose of RYBREVANT®.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

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