The OncFive: Top Oncology Articles for the Week of 7/20

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 Issues CRL for RP1 Plus Nivolumab for Advanced Melanoma

The FDA has issued a complete response letter (CRL) for the biologics license application seeking approval of vusolimogene oderparepvec (RP1) plus nivolumab (Opdivo) for PD-1–refractory advanced melanoma, citing that the phase 1/2 IGNYTE trial (NCT03767348) was not adequate to support approval due to patient heterogeneity and study design limitations. Despite a confirmed overall response rate (ORR) of 33.6% per mRECIST 1.1 criteria in the trial and no new safety concerns, the FDA could not interpret the data sufficiently to meet the regulatory standard. The CRL also raised concerns about the confirmatory trial design, specifically regarding the contribution of components. Replimune, the drug developer, shared plans to request a Type A meeting with the regulatory agency to determine a path forward, including the potential for accelerated approval. The combination continues to be evaluated in the phase 3 IGNYTE-3 trial (NCT06264180) in a more narrowly defined patient population.

FDA Tentatively Approves Generic Ibrutinib Tablets for B-Cell Malignancies

The regulatory agency has granted tentative approval to a generic tablet formulation of ibrutinib (Imbruvica), developed by Zydus Lifesciences, for the treatment of patients with select B-cell malignancies. The approval covers 140-, 280-, and 420-mg tablets, matching the dosages of the reference product. The BTK inhibitor remains indicated for adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with or without 17p deletion, adult patients with Waldenström macroglobulinemia, and adults and pediatric patients at least 1 year of age with chronic graft-vs-host disease after progression on systemic treatment. The generic is not currently approved for previously withdrawn indications, such as those in mantle cell lymphoma and marginal zone lymphoma, which were removed voluntarily in 2023. Final marketing of the generic product may depend on the expiration of existing patents or exclusivities for the branded product.

First-Line Osimertinib Plus Chemo Boosts OS in EGFR+ NSCLC

The final overall survival (OS) analysis from the phase 3 FLAURA2 trial (NCT04035486) showed that adding chemotherapy to osimertinib (Tagrisso) significantly improved OS vs osimertinib alone in patients with EGFR-mutated, locally advanced or metastatic non–small cell lung cancer. These data align with earlier results and will be shared at a future medical meeting. The findings support the February 2024 FDA approval of the combination regimen for frontline use in patients with EGFR exon 19 deletions or exon 21 L858R mutations. Previous findings from the trial showed that the combination significantly improved progression-free survival compared with monotherapy at 25.5 months vs 16.7 months, respectively (HR, 0.62). The regimen had a manageable safety profile, with common adverse effects (AEs) including myelosuppression, rash, diarrhea, and nail toxicity.

Cellular Therapies Begin to Make Their Mark in Solid Tumors

Cellular therapies have transformed hematologic malignancies, and 2024 marked a major turning point for their integration into solid tumors, with the first FDA approvals of T-cell–redirecting agents in this space. Approvals included lifileucel (Amtagvi) for unresectable/metastatic melanoma, afamitresgene autoleucel (Tecelra) for synovial sarcoma, and tarlatamab-dlle (Imdelltra) for small cell lung cancer. Despite historical challenges such as antigen heterogeneity and toxicity, ongoing innovation is addressing these barriers, with additional agents like ALLO-316 in renal cell carcinoma, xaluritamig (AMG 509) in prostate cancer, and satricabtagene autoleucel (CT041) in gastric/gastroestophageal junction cancer demonstrating promising early-phase results. Investigators are refining target selection and safety, fueling enthusiasm for future frontline use of these therapies in solid tumors. Experts say the potential durability of response and quality-of-life improvements could mirror the success seen in blood cancers. Sign up to access this exclusive feature, which includes insights from 4 experts.

FDA Grants Fast Track Status to VS-7375 for KRAS G12D–Mutated Advanced Pancreatic Cancer

The FDA has granted fast track designation to VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, for use as a potential therapeutic option in locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) in both the frontline and previously treated settings. In a phase 1/2 trial (NCT06500676) done in China, VS-7375 showed an ORR of 52% and a 100% disease control rate among 23 efficacy-evaluable patients with PDAC. No dose-limiting toxicities were reported, and the most common treatment-related AEs (TRAEs) included diarrhea, nausea, and vomiting; grade 3/4 TRAEs occurred in 29% of patients. Verastem Oncology, the drug developer, is also evaluating the agent in a US phase 1/2a trial (NCT07020221); it is also being explored in combination studies in colorectal and lung cancers.