Highlights from AACR 

Why it’s important  

New findings from a multi-institutional study suggest that the immunotherapy drug, dostarlimab, may allow some patients with mismatch repair-deficient (dMMR) gastrointestinal cancers to avoid surgery altogether. Among 103 patients with gastrointestinal cancers, 80%, including all 49 patients with rectal cancer, achieved complete response without chemotherapy, radiation, or surgery. These results reinforce the clinical value of biomarker-driven treatment decisions and highlight the need for robust regulatory frameworks that ensure diagnostic test accuracy, consistency, and reliability across settings.    

FDA/Policy Update May 20-21, 2025: Meeting of the Oncologic Drugs Advisory Committee 

Day 1 (May 20, 2025):  ODAC reviewed two applications for blood cancers, bringing attention to the growing significance of protocol-defined disease criteria and population relevance, study generalizability in clinical trials, and support for well-substantiated earlier treatment approaches in high-risk, asymptomatic patients. 

Session 1: The committee voted 8–1 against the applicability of Genentech’s Columvi (glofitamab-gxbm) trial results to the U.S. patient population with diffuse large B-cell lymphoma (DLBCL), despite the study meeting its primary endpoint.

Why it’s important 

• This decision wasn’t about the science alone. It was about relevance (whether trial results largely driven by patients outside of the U.S. can guide care inside it).  

• When clinical trials are not designed with population relevance in mind, it can limit confidence in how findings translate to real-world care and patient access. In this trial, only 9% of trial participants were enrolled in the U.S., survival outcomes varied by region, and the comparator regimen is rarely used in U.S. clinical practice (i.e., in 2-8% of patients). Together these factors raised questions about how applicable the trial is to U.S. patients and clinical practice.  

Session 2: The committee voted 6–2 in favor of the benefit-risk profile of DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) as monotherapy for high-risk smoldering multiple myeloma (HR-SMM). 

Why it’s important 

• Typically, patients with HR-SMM are monitored until disease progression. Darzalex Faspro (daratumumab and hyaluronidase-fihj) received support for use in HR-SMM and could become the first approved therapy to delay progression in this early-stage condition.  

Day 2 (May 21, 2025): ODAC issued two negative votes—5–4 against UroGen’s UGN-102 (mitomycin) for low-grade intermediate-risk non–muscle invasive bladder cancer, and 8–0 against expanding Pfizer’s Talzenna (talazoparib) in combination with enzalutamide to a broader metastatic castration-resistant prostate cancer (mCRPC) population.  Why it’s important 

• UGN-102 (mitomycin) faced skepticism due to its single-arm design and lack of a control group, limiting confidence in the observed treatment effect. 

• Talzenna (talazoparib), when used with enzalutamide, was not supported for broader mCRPC use due to insufficient benefit in patients without homologous recombination repair (HRR) mutations. 

Highlight from ASCO Project FrontRunner drug approval

Why it’s important 

Pfizer’s Braftovi (encorafenib) combination therapy for BRAF V600E-mutant metastatic colorectal cancer has shown unprecedented survival benefits in the Phase 3 BREAKWATER trial, doubling median overall survival compared to standard treatment. The regimen received accelerated approval from the FDA under Project FrontRunner and is now being considered for full approval based on updated survival data. This marks one of the first major examples of a single Phase 3 trial supporting both accelerated and full approval, reflecting a shift in regulatory strategy. These results may establish a new standard of care and highlight the evolving role of the Accelerated Approval pathway in advancing oncology treatment. 

Key data presented at the 2025 ASCO Annual Meeting: 

• Overall Survival (OS): The Braftovi (encorafenib) regimen reduced the risk of death by 51%, with median OS reaching 30.3 months versus 15.1 months for standard chemotherapy. 

• Progression-Free Survival (PFS): Patients receiving the Braftovi (encorafenib) combination had a median PFS of 12.8 months, compared to 7.1 months in the control group—a 47% reduction in the risk of progression or death. 

• Objective Response Rate (ORR): The therapy achieved a 61% ORR, significantly higher than the 40% seen with standard chemotherapy. 

These results, shared during ASCO and published in the New England Journal of Medicine, underscore the clinical impact of this combination and exemplify the aims of Project FrontRunner: to bring transformative treatments to patients faster through earlier, well-structured trials.