May FDA Approvals in Oncology: Firsts in PPGL, Anal Cancer, and More

The FDA granted 2 accelerated and 2 standard approvals to oncology therapies in May.

Throughout National Nurses Month, 4 cancer therapies were given FDA regular or accelerated approval, spanning diseases including ovarian, head and neck, lung, and anal cancers.

These treatments will offer patients with cancer more options, including 2 first-oral treatments approved in paraganglioma or pheochromocytoma and anal cancer. Additionally, 2 of the therapies approved last month were given accelerated approval, indicating the high priority of these treatments in treating diseases with urgent or unmet needs.

Below is a comprehensive list of cancer therapies approved in May, including efficacy findings and common adverse events (AEs).

Avutometinib/Defactinib in KRAS-mutated Low-Grade Serous Ovarian Cancer

On May 8, the FDA granted accelerated approval to avutometinib (VS-6766) plus defactinib (VS-6063) for the treatment of adult patients with KRAS-mutated recurrent, low-grade serous ovarian cancer following previous systemic therapy, based on data from the open-label, multicenter phase 2 RAMP-201 trial (NCT04625270).¹

Patients who received avutometinib plus defactinib had a confirmed overall response rate (ORR) of 44% (95% CI, 31%-58%) and a duration of response (DOR) of 3.3 months to 31.1 months with the combination.

The most frequent AEs, which occurred in at least 25% of patients, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, emesis, hyperbilirubinemia, hypertriglyceridemia, lymphocytopenia, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, thrombocytopenia, constipation, dry skin, dyspnea, cough, urinary tract infection, and neutropenia.

Patients evaluated in RAMP-201 had received at least 1 line of systemic therapy previously, which was required to include a platinum-based regimen; prospective local testing of tumor tissue was used to confirm patients’ KRAS mutation.

Belzutifan for Pheochromocytoma or Paraganglioma

The FDA granted its first approval of an oral therapy for pheochromocytoma or paraganglioma (PPGL) to belzutifan (Welireg) for the treatment of adult and pediatric patients aged 12 years or older with locally advanced, unresectable, or metastatic disease, according to an announcement from the FDA on May 14.² The approval was based on results from the multi-cohort, open-label LITESPARK-015 trial (NCT04924075) in patients with PPGL with primary trial end points of ORR and DOR, along with the number of patients with a reduction in one or more antihypertensive medications of at least 50% for at least 6 months.

The ORR for belzutifan in patients with PPGL was 26% (95% CI, 17%-38%; n = 72). The median DOR for these patients was 20.4 months (95% CI, 8.3-NR). Out of 60 patients who were taking antihypertensive medications at intake, 19 (32%; 95% CI, 20%-45%) had a reduction of at least 50% in at least 1 antihypertensive medication sustained for 6 months or longer.

The most common AEs, which were reported in at least 25% of patients, including laboratory abnormalities, were anemia, fatigue, musculoskeletal pain, lymphocytopenia, increased alanine aminotransferase, increased aspartate aminotransferase, hypercalcemia, dyspnea, hyperkalemia, leukopenia, headache, increased alkaline phosphatase, dizziness, and nausea.

Telisotuzumab Vedotin for Non–Small Cell Lung Cancer

The FDA granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis) for use in adult patients with locally advanced and metastatic non-squamous, non-small cell lung cancer who have received prior systemic therapy and have high c-Met protein overexpression, according to a news release published on May 14 by AbbVie, the drug’s developer.³

The approval is based on data from the phase 2 LUMINOSITY study (NCT03539536). Patients on the trial with high c-Met expression in NSCLC (n = 84) saw a 35% ORR rate (95% CI, 24%-46%). The median DOR was 7.2 months (95% CI, 4.2-12).

The most common AEs, present in at least 20% of patients, were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most frequent laboratory abnormalities of grade 3 or 4, reported in at least 2% of patients, were lymphocytopenia, hyperglycemia, increased alanine aminotransferase, increased gamma glutamyl transferase, hypophosphatemia, hyponatremia, decreased hemoglobin, and hypocalcemia.

Retifanlimab in Advanced Squamous Cell Anal Cancer

Retifanlimab-dlwr (Zynyz) was granted approval from the FDA for the treatment of locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC), both in combination chemotherapy and as a single agent, on May 15, making it the first oral therapy approved for anal cancer, per an announcement from the drug’s developer, Incyte.⁴

The therapy is approved in combination with carboplatin and with paclitaxel for the first-line treatment of patients with inoperable disease and as a monotherapy for patients who have progressed on or are intolerant to platinum-based chemotherapy.

Findings from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429) on retifanlimab combined with chemotherapy demonstrated a statistically significant 37% reduction of risk of progression or death and a median progression free survival (PFS) of 9.3 months (95% CI, 7.5-11.3) vs 7.4 months with placebo plus chemotherapy (95% CI, 7.1-7.7; P = .0006, n = 154).⁵ The median follow-up times for PFS were 7.6 months (range, 0.0-33.9) and 7.1 months (range, 0.0-27.4), respectively.

Data from the phase 2 POD1UM-202 trial (NCT03597295), investigating retifanlimab as a monotherapy, demonstrated that at a median follow-up of 7.1 months (range, 0.9-19.4) retifanlimab yielded an ORR of 13.8% (95% CI, 7.6%-22.5%), including 1 complete response and 12 partial responses (n = 94). Median DOR was 9.5 months (range, 5.6 month-NE), and median PFS and OS were 2.3 (95% CI, 1.9-3.6) and 10.1 (95% CI, 7.9-NE), respectively.⁶

Treatment-emergent adverse effects (TEAEs) of any grade occurred in all patients in the retifanlimab and placebo arms in POD1UM-303/InterAACT2.⁵ Patients in both arms experienced grade 3 or higher TEAEs (83.1% vs 75.0%), grade 5 TEAEs (2.6% vs 0.7%), serious AEs (47.4% vs 38.8%), treatment-related serious AEs (16.2% vs 6.6%), immune-related AEs (46.1% vs 23.7%), and AEs leading to treatment discontinuation (11.0% vs 2.6%). At the data cutoff, 58.4% of patients in the investigation arm remained on the study.

In POD1UM-202, TEAEs occurred in 90 patients (95.7%), the most common of which being pruritic (11.7%), fatigue (9.6%), diarrhea (8.5%), asthenia (7.4%), nausea (6.4%), increased aspartate aminotransferase, and hypothyroidism (each 5.3%).⁴ Fifty-five patients had TEAEs grade 3 or higher.⁶

References

1. FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. FDA. May 8, 2025. Accessed June 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low
2. FDA approves belzutifan for pheochromocytoma or paraganglioma. FDA. May 14, 2025. Accessed June 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pheochromocytoma-or-paraganglioma
3. U.S. FDA approves EMRELIS (telisotuzumab vedotin-tllv) for adults with previously treated advanced non-small cell lung cancer (NSCLC) with high c-Met protein overexpression. News release. AbbVie. May 14, 2025. Accessed May 14, 2025. https://news.abbvie.com/2025-05-14-U-S-FDA-Approves-EMRELIS-TM-telisotuzumab-vedotin-tllv-for-Adults-With-Previously-Treated-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-With-High-c-Met-Protein-Overexpression
4. Incyte announces FDA approval of Zynyz (retifanlimab-dlwr) making it the first and only approved first-line treatment for advanced anal cancer patients in the United States. News release. Incyte Corporation. May 15, 2025. Accessed June 6, 2025. https://www.businesswire.com/news/home/20250508024371/en/Incyte-Announces-FDA-Approval-of-Zynyz-retifanlimab-dlwr-Making-it-the-First-and-Only-Approved-First-Line-Treatment-for-Advanced-Anal-Cancer-Patients-in-the-United-States
5. Rao S, Samalin-Scalzi E, Evesque L, et al. POD1UM-303/InterAACT 2: phase 3 study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA2.
6. Rao S, Anandappa G, Capdevila J, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. 2022;7(4):100529. doi:10.1016/j.esmoop.2022.100529