OncLive’s FDA Approval Report: The Regulatory Rundown for May 2025

FDA Approval Roundup: May

Below is your guide to all the oncologic therapeutic options cleared by the FDA in May 2025. The roundup provides everything you need to know, right at your fingertips—all the topline data that supported the decisions and expert insights contextualizing what they mean for clinical practice.

5/8: Avutometinib Plus Defactinib in KRAS-Mutated Recurrent Low-Grade Serous Ovarian Cancer

Indication: The regulatory agency granted accelerated approval to the combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack) for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.

Supporting Data: The decision was based on data from the phase 2 RAMP-201 trial (NCT04625270), in which the combination demonstrated a confirmed overall response rate (ORR) of 44% (95% CI, 31%-58%), including a 3.5% complete response rate and a 40% partial response (PR) rate. The duration of response (DOR) ranged from 3.3 to 31.1 months. The regimen was generally well tolerated, with serious adverse effects (AEs) reported in 32% of patients and treatment discontinuation due to toxicity occurring in 14% of patients.

Bradley Monk, MD, FACOG, FACS

Significance: This is the first FDA-approved treatment for LGSOC, addressing a major unmet need in a rare, recurrent, and historically treatment-resistant subtype of ovarian cancer. The regimen offers a targeted therapy option for patients with KRAS mutations and is expected to become a new standard of care, pending confirmation from the ongoing phase 3 RAMP 301 trial (NCT06072781).

“This is the first time we have ever had an FDA approval for LGSOC, a rare variant of ovarian cancer. Generally, we think of ovarian cancer as being high grade serous, but low-grade serous cancer is a [disease subtype] where 70% of the tumors are driven by RAS and [are] part of the MAPK pathway,” Bradley Monk, MD, FACOG, FACS, of Florida Cancer Specialists & Research Institute, told OncLive. “[Approximately] 30% of those tumors are KRAS mutant, [and] there are other mutations—including NRAS, BRAF, NF1, and other RAS pathway–associated gene mutations. However, KRAS mutations are particularly important, and this accelerated approval is [for agents targeting] tumors with KRAS mutations.”

We also spoke with Rachel N. Grisham, MD, of Memorial Sloan Kettering Cancer Center Westchester, about the significance of the approval:

OTHER RELATED COVERAGE

Ritu Salani, MD, MBA

• In a past interview, Ritu Salani, MD, MBA, of UCLA Health, discussed the significance of trials examining avutometinib plus defactinib and excitement antibody-drug conjugates have generated in ovarian cancer.
• In a past clinical trial spotlight article, which features insights from Jubilee Brown, MD, of Atrium Health Levine Cancer Institute, we take a deep dive into the confirmatory RAMP 301 trial and all the data that paved the way to its launch.
• In a prior OncLive On Air episode, Brown discussed how the RAS/MAPK pathway contributes to LGSOC, unmet needs for patients with this disease, and the rationale for RAMP-301 trial.
• Premal Thaker, MD, MS, of Siteman Cancer Center, also commented on the RAMP-301 study in an interview last year.

5/14: Belzutifan in Advanced Pheochromocytoma and Paraganglioma

Indication: TheHIF-2α inhibitor belzutifan (Welireg) was cleared by the FDA for the treatment of adult and pediatric patients aged 12 years or older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma.

Supporting Data: The decision was based on findings from the phase 2 LITESPARK-015 trial (NCT04924075).In cohort A1 (n = 72), belzutifan achieved an ORR of 26% (95% CI, 17%-38%) with a median DOR of 20.4 months. Over half of the responders (53%) maintained a response for at least 12 months. The median time to response (TTR) was 11 months. Notably,32% of patients reduced antihypertensive medication use by at least 50% for at least 6 months, suggesting a meaningful impact on symptom control.

Significance: Belzutifan offers a targeted, non-surgical treatment option for a rare and difficult-to-treat group of tumors with limited approved therapies. Its approval builds on the agent’s growing role across Von Hippel-Lindau (VHL)–associated and clear cell renal cell carcinoma (RCC) indications. The durable responses and potential for blood pressure stabilization represent clinically meaningful benefits for patients with advanced pheochromocytoma or paraganglioma.

“The fact that we now have an FDA-approved drug option that was prospectively evaluated in a very strong clinical trial is great, and I think it will mean a lot to patients and providers of this patient population,” Kimberly Perez, MD, of Dana-Farber Cancer Institute, told OncLive. She further discussed the clinical implications of the approval:

OTHER RELATED COVERAGE

• The agent was granted priority review for this indication back in January 2025 and was assigned a decision date of May 26, 2025. Belzutifan was approved 12 days ahead of schedule.
• In December 2023, the FDA approved belzutifan for the treatment of patients with advanced RCC following a PD-1 or PD-L1 inhibitor and a VEGF TKI.
• In August 2021, the regulatory agency cleared belzutifan for use in adult patients with VHL disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery.

5/14: Telisotuzumab Vedotin in Pretreated Advanced NSCLC With c-MET Overexpression

Indication: The FDA granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis) for adult patients with locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC) with high c-MET protein overexpression, defined as immunohistochemistry 3+ staining on at least 50% of tumor cells, who have received a prior systemic therapy.

Supporting Data: Approval was based on the phase 2 LUMINOSITY trial (NCT03539536), in which patients with high c-MET protein expression (n = 84) achieved an ORR of 35% (95% CI, 24%-46%), with a median DOR of 7.2 months (95% CI, 4.2-12). All responses were PRs, and 21% of patients maintained their response for at least 12 months. Treatment was well tolerated overall; key AEs included peripheral neuropathy, fatigue, and peripheral edema.

Jonathan Goldman, MD

Significance: Telisotuzumab vedotin is the first FDA-approved therapy specifically targeting high c-MET protein overexpression in NSCLC, addressing a distinct subset of patients with limited treatment options. This decision adds to the expanding class of antibody-drug conjugates (ADCs) in lung cancer and offers a personalized therapy for patients with poor prognosis. Ongoing phase 3 evaluation in TeliMET NSCLC-01 (NCT04928846) will further define its role vs standard chemotherapy.

“We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes,” Jonathan Goldman, MD, of UCLA, stated in a news release. “People with c-Met overexpressing NSCLC have poor prognosis and limited treatment options, and Emrelis is a first-in-class ADC that can address a critical unmet need for this patient population.”

OTHER RELATED COVERAGE

Stephen V. Liu, MD

• In January 2022, the FDA granted breakthrough therapy designation to telisotuzumab vedotin for use in patients with advanced or metastatic EGFR wild-type, nonsquamous NSCLC who have high levels of c-MET overexpression and whose disease progressed on or following platinum-based chemotherapy. The decision was supported by early LUMINOSITY findings.
• In a past interview, Stephen V. Liu, MD, of Georgetown University, discussed the future of MET-targeted therapies in NSCLC based on the FDA breakthrough therapy designation of telisotuzumab vedotin.
• In another prior interview, Karen L. Reckamp, MD, MS, of Cedars-Sinai Medical Center, highlighted ADCs in lung cancer, spotlighting the development of patritumab deruxtecan and telisotuzumab vedotin.
• Past data from a phase 1b study (NCT02099058) also found that when telisotuzumab vedotin was paired with erlotinib (Tarceva), it led to a 30.6% ORR in patients with advanced, EGFR-mutated, c-MET–positive NSCLC who were contraindicated for surgery or other approved therapies.

5/15: Retifanlimab in Advanced Anal Cancer

Indication: The FDA has approved retifanlimab-dlwr (Zynyz) in combination with carboplatin and paclitaxel as a first-line treatment for adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The agent was also cleared as monotherapy for patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.

Supporting Data: The combination indication was based on results from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429), which demonstrated a median progression-free survival (PFS) of 9.3 months (95% CI, 7.5-11.3) with retifanlimab plus chemotherapy vs 7.4 months (95% CI, 7.1-7.7) for placebo plus chemotherapy (HR, 0.63; 95% CI, 0.47-0.84; P = .0006). Median overall survival (OS) was 29.2 months (95% CI, 24.2-not evaluable) vs 23.0 months (95% CI, 15.1-27.9), respectively (HR, 0.70; 95% CI, 0.49-1.01; P = .0273). The combination led to an ORR of 56% (95% CI, 48%-64%) and a median DOR of 14.0 months (95% CI, 8.6-22.2). Serious AEs occurred in 47% of patients, most commonly sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%), and vomiting (2.6%).

For the monotherapy indication, the phase 2 POD1UM-202 trial (NCT03597295) showed an ORR of 14% (95% CI, 8%-23%) and a disease control rate of 49% in patients previously treated with platinum-based chemotherapy. Serious AEs occurred in 40% of patients. The safety profile was consistent with that of PD-1 inhibitors.

Significance: Retifanlimab is the first PD-1 inhibitor approved for patients with SCAC, offering new treatment options in both the frontline and previously treated settings.

“This FDA approval [indicates] an immunotherapy drug for the first time, and [this is] an area where there is a significant unmet need,” Marwan Fakih, MD, of City of Hope, told OncLive. He further discussed the clinical relevance of the decision:

OTHER RELATED COVERAGE

• The biologics license application seeking the approval of retifanlimab in adult patients with locally advanced or metastatic SCAC who were intolerant of or who had progressed on platinum-based chemotherapy was first granted priority review by the FDA in January 2021.

Sheela Rao, MBBS, MD, FRCP

• In June 2021, the FDA’s Oncologic Drugs Advisory Committee voted 13 to 4 to hold off on a decision regarding accelerated approval of the agent. They cited that it would be “premature” to issue a ruling based on the data available at the time, and they preferred to wait for results from a randomized clinical trial before deciding.
• Thus, later that month, the regulatory agency issued a complete response letter to Incyte Corporation stating that it could not approve the retifanlimab BLA.
• In September 2024, the phase 3 POD1UM-303/InterAACT 2 study met its primary end point, with data showing a significant PFS benefit with retifanlimab paired with carboplatin and paclitaxel vs carboplatin/paclitaxel alone in patients with recurrent or metastatic SCAC who had no prior chemotherapy. Data were shared at the 2024 ESMO Congress.
• In December 2024, ASCO released a new systemic therapy guideline for stage I to II anal cancer, which sought to offer evidence-based guidance through a systematic review of 3 randomized controlled trials and 3 nonrandomized studies of relevant interventions. It was projected that a potential new standard of care could emerge with retifanlimab.
• In a past interview, Sheela Rao, MBBS, MD, FRCP, of Royal Marsden Hospital, discussed the rationale for POD1UM-303, the significance of the retifanlimab data shared during the 2024 ESMO Congress, and future directions for the agent in SCAC.

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