J&J(JNJ) Prnewswire·2024-09-14 13:45Clinical Trial Results - RYBREVANT® combined with chemotherapy (mFOLFOX6 or FOLFIRI) demonstrated promising antitumor activity in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) who had not previously received anti-EGFR therapy, with a median duration of response of 7.4 months and a median progression-free survival of 7.5 months [1] - The overall response rate (ORR) was 49%, with disease control observed in 88% of patients, and 21% of patients proceeded to curative-intent surgery due to strong antitumor activity [1] - The safety profile of RYBREVANT® plus chemotherapy was manageable, with no new safety signals observed, and the most frequent adverse events were neutropenia, rash, stomatitis, infusion-related reactions, and diarrhea [1] Study Design and Patient Population - OrigAMI-1 is an open-label Phase 1b/2 study assessing the efficacy and safety of RYBREVANT® plus mFOLFOX6 or FOLFIRI in anti-EGFR-naïve RAS/BRAF WT mCRC patients, with 43 patients treated in the study [2][3] - Patients were either in their first (26%) or second line (74%) of treatment for mCRC and had not been treated with specific anti-EGFR therapies [1] RYBREVANT® Overview - RYBREVANT® is a fully-human bispecific antibody targeting EGFR and MET, approved for the treatment of NSCLC with EGFR exon 20 insertion mutations in the U.S., Europe, and other markets [4] - It is also approved in combination with chemotherapy for first-line treatment of NSCLC with EGFR exon 20 insertion mutations and in combination with LAZCLUZE™ for NSCLC with EGFR exon 19 deletions or L858R substitution mutations [4][5] Regulatory Submissions and Approvals - Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA for RYBREVANT® in combination with chemotherapy for EGFR-mutated NSCLC patients who progressed on or after osimertinib, with this indication approved in Europe in August 2024 [5] - A BLA was submitted to the U.S. FDA for the subcutaneous formulation of RYBREVANT® in combination with LAZCLUZE™ for NSCLC indications, with a similar submission made to the EMA [6] Colorectal Cancer Background - Colorectal cancer is the third most common cancer globally, accounting for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths worldwide [8] - Left-sided colorectal cancer represents approximately 65% of cases, with around half of patients having mutations in the RAS genes, particularly KRAS, which influences treatment strategies [8] Ongoing Clinical Trials - RYBREVANT® is being studied in multiple clinical trials, including Phase 3 studies like MARIPOSA, MARIPOSA-2, PAPILLON, and PALOMA-3, evaluating its efficacy in various NSCLC settings [6][7] - Other trials include Phase 1/2 studies like METalmark, PolyDamas, and swalloWTail, exploring combination therapies and new formulations for NSCLC and other solid tumors [7]