The OncFive: Top Oncology Articles for the Week of 8/31

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 Grants Type A Meeting to Discuss RP1 Plus Nivolumab in Advanced Melanoma

The FDA has scheduled a Type A meeting with Replimune to discuss the complete response letter issued for the biologics license application (BLA) seeking approval of vusolimogene oderparepvec (RP1) plus nivolumab (Opdivo) in patients with previously treated advanced melanoma. The letter, issued on July 22, 2025, stated that the phase 1/2 IGNYTE trial (NCT03767348) did not constitute a substantial, well-controlled study to support approval, citing heterogeneity in the patient population. No safety concerns were raised. Replimune submitted a briefing book addressing the agency’s feedback, including prior agreements on trial population, definitions of PD-1 resistance, and confirmatory trial design, along with new analyses of the BLA data. IGNYTE data showed that the regimen elicited an overall response rate (ORR) of 33.6% and a complete response rate of 15.0% at a median follow-up of 15.4 months.

OncLive’s August Roundup of Key FDA Approvals in Oncology: 3 Decisions to Know

In August 2025, the FDA cleared multiple oncologic therapies, including dordaviprone (Modeyso; formerly ONC201), zongertinib (Hernexeos), and a 3-month depot formulation of leuprolide mesylate (Camcevi ETM). Dordaviprone received accelerated approval for patients with H3K27M-mutant diffuse midline glioma based on pooled data from 5 trials (NCT02525692, NCT03295396, NCT03416530, NCT03134131, NCT05392374), which showed an ORR of 22% and durable benefit in responders. Zongertinib was granted accelerated approval for previously treated HER2 TKD–mutant nonsquamous non–small cell lung cancer (NSCLC). This decision was supported by findings from the phase 1 Beamion LUNG-1 trial (NCT04886804), which demonstrated an ORR of 75% in patients without prior HER2-directed therapy and 44% in those previously exposed to HER2-targeted ADCs. The agency also cleared a 3-month, 21-mg depot formulation of leuprolide mesylate for advanced prostate cancer; this approval was supported by data from the phase 3 trial (NCT03261999), in which 97.9% of patients achieved sustained testosterone suppression. Read the full roundup.

TT125-802 Earns FDA Fast Track Designations for EGFR+ and KRAS G12C+ Advanced NSCLC

The FDA has granted two fast track designations to the small molecule CBP/p300 bromodomain inhibitor TT125-802 for patients with locally advanced or metastatic NSCLC harboring either EGFR exon 19 deletions or exon 21 L858R substitutions following progression on previous EGFR inhibitors, and for those with KRAS G12C–mutated NSCLC following progression on previous KRAS G12C inhibitors. Data from the phase 1 TT-CSP-001 trial (NCT06403436) shared at the 2025 ASCO Annual Meeting showed clinical benefit lasting more than 6 months in 7 of 26 patients with advanced solid tumors. The agent was generally well tolerated, with one dose-limiting toxicity of grade 3 hyperglycemia at 60 mg twice daily. Most (98%) treatment-related adverse effects (AEs) were grade 1 or 2, and no cases of thrombocytopenia were reported. The most common AEs comprised dysgeusia, hyperglycemia, anemia, elevated liver and pancreatic enzymes, stomatitis, fatigue, and decreased appetite.

FDA Grants Breakthrough Device Designation to Haystack MRD ctDNA Liquid Biopsy for Stage II CRC

The FDA has awarded breakthrough device designation to the Haystack MRD® test, a circulating tumor DNA (ctDNA) liquid biopsy designed to identify patients with stage II colorectal cancer (CRC) who are minimal residual disease positive and may benefit from adjuvant therapy after surgery. The test’s clinical utility has been demonstrated in the pivotal phase 2 DYNAMIC study (ACTRN12615000381583), which enrolled 455 patients. Data indicated that a ctDNA-guided strategy reduced chemotherapy use to 15% vs 28% in standard-of-care management without compromising 2-year recurrence-free survival. The ongoing phase 2/3 DYNAMIC-III trial (ACTRN12617001566325) is examining ctDNA-guided treatment escalation and de-escalation strategies in resected stage III CRC. Haystack MRD is already being leveraged in several clinical trials and research collaborations across the US, Canada, and Australia, supporting personalized adjuvant therapy decisions.

Development to Discontinue for ZW171 in Gynecologic, Thoracic, and GI Cancer

Zymeworks announced it will discontinue development of the mesothelin-directed T-cell engager ZW171 for patients with gynecologic, thoracic, and gastrointestinal cancers. The decision followed data from planned cohorts of a phase 1 trial (NCT06523803), which examined the agent in ovarian cancer and NSCLC, and indicated the risk–benefit profile would not support further study of the agent as monotherapy. Patients currently on ZW171 can continue treatment at investigator's discretion, and those who have discontinued will remain under safety follow-up. The phase 1 trial had been assessing safety, dose-limiting toxicities, and preliminary efficacy outcomes, such as ORR, duration of response, and progression-free survival.