Welcome to OncLive®’s OncFive!
Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.
Here’s what you may have missed this week:
FDA Approves Avutometinib Plus Defactinib for KRAS-Mutated Recurrent Low-Grade Serous Ovarian Cancer
The FDA has granted accelerated approval to avutometinib plus defactinib (Avmapki Fakzynja Co-pack) for adult patients with recurrent KRAS-mutated low-grade serous ovarian cancer (LGSOC) following prior systemic therapy. The decision was based on phase 2 RAMP-201 (NCT04625270) data showing a confirmed overall response rate of 44% (95% CI, 31%-58%) and a median duration of response ranging from 3.3 to 31.1 months. Dose interruptions and reductions due to an adverse effect (AE) were experienced by 84% and 44% of patients, respectively. AEs led to permanent discontinuation of the doublet for 14% of patients. This marks the first FDA-approved therapy for KRAS-mutated LGSOC and establishes a new standard of care, with the confirmatory phase 3 RAMP 301 trial (NCT06072781) currently underway.
T-DXd Followed by THP Improves pCR Rate in HER2+ Early Breast Cancer
The phase 3 DESTINY-Breast11 trial (NCT05113251) showed that neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by trastuzumab (Herceptin), pertuzumab (Perjeta), and paclitaxel (THP) significantly improved pathologic complete response (pCR) rates compared with standard dose-dense doxorubicin and cyclophosphamide followed by THP in patients with high-risk, HER2-positive early-stage breast cancer. Early event-free survival data also favored the T-DXd–based regimen, although results were not yet mature. Based on these findings, T-DXd may represent a promising shift in the neoadjuvant treatment paradigm, moving this targeted agent earlier in the disease course. Full data will be presented at the 2025 ASCO Annual Meeting, with potential regulatory submissions to follow.
Durvalumab Plus BCG Improves DFS in High-Risk Non–Muscle-Invasive Bladder Cancer
Topline results from the phase 3 POTOMAC trial (NCT03528694) showed that adding durvalumab (Imfinzi) to BCG induction and maintenance therapy significantly improved disease-free survival (DFS) in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) compared with BCG alone. The safety profile was consistent with prior findings, with no new safety signals and no compromise in patients’ ability to complete BCG therapy. The investigational arm assessing durvalumab with BCG induction only did not meet the DFS endpoint, highlighting the importance of continued maintenance. These findings may support a new immunotherapy-based approach for high-risk NMIBC and will be submitted to regulatory agencies for potential approval.
FDA Issues Refusal to File Letter for Nogapendekin Alfa Inbakicept sBLA in BCG-Unresponsive Papillary NMIBC
The FDA issued a Refusal to File (RTF) letter for ImmunityBio’s supplemental biologics license application seeking approval of nogapendekin alfa inbakicept (Anktiva) plus BCG for patients with BCG-unresponsive NMIBC with papillary tumors without carcinoma in situ (CIS). This decision came despite prior guidance from FDA leadership encouraging submission based on promising results from cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825), which showed strong disease-specific survival and cystectomy-free rates. ImmunityBio is pursuing a Type A meeting with the agency to clarify the discrepancy and determine a path forward. Importantly, the RTF does not affect the FDA’s April 2024 approval of the combination for BCG-unresponsive NMIBC with CIS, granted based on cohort A data.
Poll Results Punctuate Key Lung Cancer Abstracts Driving Intrigue Ahead of ASCO 2025
Leading into the 2025 ASCO Annual Meeting, lung cancer experts are focused on several pivotal trials that could influence future treatment standards. A social media poll highlighted two late-breaking abstracts—LBA8010 (updated survival/biomarker data from CheckMate 77T [NCT04025879]) and LBA8000 (overall survival from CheckMate 816 [NCT02998528])—as the most anticipated. Other highly anticipated presentations include LBA8505 (savolitinib [Orpathys] plus osimertinib [Tagrisso] vs chemotherapy in EGFR/MET-altered non–small cell lung cancer [NSCLC]), 8015 (neoadjuvant alectinib [Alecensa] in ALK+ NSCLC), 8639 (MARIPOSA-2 [NCT04988295] outcomes by osimertinib resistance mechanisms), 8001 (NeoADAURA [NCT04351555]: neoadjuvant osimertinib with or without chemotherapy), 8500 (adagrasib [Krazati] plus pembrolizumab [Keytruda] in KRAS G12C–mutated NSCLC), and 8646 (RET inhibitor rechallenge in RET-rearranged NSCLC). These presentations span a range of therapeutic strategies and biomarker-defined subgroups, signaling major updates in the personalized treatment of NSCLC.
Leave a Reply