Q2 2025: 7 FDA Decisions to Watch in the Realm of Oncology

Following a busy first quarter marked by multiple high-impact approvals, the momentum heading into Q2 2025 is strong. Some Q1 highlights? Acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan) redefined standard first-line treatment for older patients with mantle cell lymphoma. In breast cancer, datopotamab deruxtecan and trastuzumab deruxtecan offer meaningful alternatives to conventional chemotherapy, including for patients with HER2-low or ultra-low disease. Durvalumab’s (Imfinzi) perioperative approval in muscle-invasive bladder cancer and lutetium Lu 177 vipivotide tetraxetan's (Pluvicto) earlier use in metastatic castration-resistant prostate cancer both signal shifts toward earlier intervention in historically difficult-to-treat settings.

With this backdrop of accelerated innovation, Q2 begins, and the oncology community is closely watching the FDA for several key regulatory decisions. With potential approvals spanning a range of therapeutic areas, the next few months could introduce new treatment options and reshape current standards of care.

Here is OncLive’s curated list of 7 FDA decisions to watch this quarter:

#1: Nivolumab Plus Ipilimumab

Drug Indication: Unresectable Hepatocellular Carcinoma
Projected Action Date: April 21, 2025

On August 21, 2024, Bristol Myers Squibb announced the FDA accepted its supplemental biologics license application (sBLA) for nivolumab (Opdivo) plus ipilimumab (Yervoy) as a first-line treatment for adults with unresectable hepatocellular carcinoma.1 The application is supported by data from the phase 3 CheckMate 9DW trial (NCT03215706) showing the combination significantly improved overall survival compared to sorafenib (Nexavar) or lenvatinib (Lenvima).

The median overall survival reached 23.7 months (95% CI, 18.8-29.4) with the doublet (n = 335) vs 20.6 months (95% CI, 17.5-22.5) with sorafenib or lenvatinib (n = 333). The objective response rate was also notably higher, at 36% (95% CI, 31%-42%) vs 13% (95% CI, 10%-17%). According to Bristol Myers Squibb, this could offer a new standard for a population with limited frontline options and growing incidence in the United States.

#2: Belzutifan

Drug Indication: Advanced Pheochromocytoma and Paraganglioma
Projected Action Date: May 26, 2025

On January 27, 2025, Merck announced the FDA granted priority review to its supplemental new drug application (sNDA) for belzutifan (Welireg) to treat patients aged 12 years and older with advanced, unresectable, or metastatic pheochromocytoma and paraganglioma.2 The submission is backed by findings from the phase 2 LITESPARK-015 trial (NCT04924075), a single-arm study evaluating belzutifan across multiple rare tumor types.

A target action date of May 26, 2025, has been set under the Prescription Drug User Fee Act (PDUFA). This marks a potential first approved treatment for these rare adrenal-related tumors in the United States. According to Merck, the designation highlights an urgent need for new therapies in this underserved patient population.

#3: UGN-102

Drug Indication: Non–Muscle Invasive Bladder Cancer
Projected Action Date: June 13, 2025

On October 15, 2024, UroGen Pharma announced the FDA accepted its NDA for UGN-102 (mitomycin) for the treatment of low-grade intermediate-risk non–muscle invasive bladder cancer.3 The submission is supported by data from three clinical trials, including the phase 3 ENVISION trial (NCT05243550), which showed a 79.6% complete response rate at 3 months and over 82% response durability at 12 months.

A PDUFA goal date has been set for June 13, 2025. UGN-102 could become the first FDA-approved therapy for this bladder cancer subtype. According to UroGen, this represents a major step forward for patients who currently face limited non-surgical options.

#4: Nivolumab Plus Ipilimumab

Drug Indication: Colorectal Cancer
Projected Action Date: June 23, 2025

On February 24, 2025, Bristol Myers Squibb announced the FDA acceptance of a sBLA for nivolumab plus ipilimumab for first-line use in adult and pediatric patients with microsatellite instability–high or mismatch repair–deficient metastatic colorectal cancer (CRC).4 Data from the phase 3 CheckMate 8HW trial (NCT04008030) demonstrated superior progression-free survival (PFS) outcomes with the combination compared with chemotherapy, with significant benefit across all lines of treatment. Updated data from the 2025 Gastrointestinal Cancers Symposium indicated that the hazard ratio for PFS was 0.62 (95% CI, 0.48-0.81; P = .0003).

According to the FDA, the sBLA has been granted breakthrough therapy designation and priority review, with a target action date of June 23, 2025. This regulatory milestone brings the potential for a new standard-of-care treatment for this patient population. The combination therapy’s safety profile was consistent with prior reports, with no new safety concerns identified.

#5: Pembrolizumab

Drug Indication: Head and Neck Squamous Cell Carcinoma
Projected Action Date: June 23, 2025

On February 25, 2025, Merck announced FDA acceptance and priority review to a sBLA seeking approval of pembrolizumab (Keytruda) as neoadjuvant treatment, then continued as adjuvant therapy paired with standard-of-care radiotherapy with or without cisplatin, and then as single-agent maintenance in patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC).5

Based on data from the prespecified first interim analysis of the phase 3 KEYNOTE-689 trial (NCT03765918), pembrolizumab showed a statistically significant improvement in event-free survival and major pathological response rate compared with standard therapy. A target action date of June 23, 2025, has been set under the PDUFA. According to Merck, this marks the first phase 3 trial to show a benefit with PD-1 inhibition in earlier-stage HNSCC.

#6: Taletrectinib

Drug Indication: ROS1+ Advanced Non–Small Cell Lung Cancer
Projected Action Date: June 23, 2025

On December 23, 2024, Nuvation Bio announced the FDA granted priority review to the NDA seeking approval of taletrectinib in patients with ROS1-positive advanced non–small cell lung cancer (NSCLC).6 Based on pooled data from the phase 2 TRUST-1 (NCT04395677) and TRUST-II (NCT04919811) trials, taletrectinib achieved an overall response rate of 88.8% (95% CI, 82.8%-93.2%) in TKI-naive patients (n = 160) and 55.8% (95% CI, 46.1%-65.1%) in those previously treated with a ROS1 TKI (n = 113).

According to Nuvation Bio, this NDA is supported by the largest ROS1-positive NSCLC dataset to date, highlighting the drug’s potential to deliver durable benefits. The FDA set a target action date of June 23, 2025.

#7: Avutometinib Plus Defactinib

Drug Indication: KRAS-Mutated Low-Grade Serous Ovarian Cancer
Projected Action Date: June 30, 2025

On January 2, 2025, Verastem Oncology announced the FDA accepted and granted priority review to the NDA seeking approval for the use of avutometinib (VS-6766) plus defactinib (VS-6063) for adult patients with recurrent KRAS-mutant low-grade serous ovarian cancer who have previously received at least 1 systemic therapy.7 Based on data from the phase 2 RAMP 201 trial (NCT04625270), the combination demonstrated a confirmed overall response rate of 44% (95% CI, 31%-58%) and a median progression-free survival of 22 months (95% CI, 11.1-36.6) in the KRAS-mutated population (n = 57).

According to Verastem, this marks a critical step toward delivering the first FDA-approved therapy for this rare and underserved patient group. The regulatory agency assigned a target action date of June 30, 2025, and does not plan to hold an advisory committee meeting.

References

1. Bristol Myers Squibb receives US Food and Drug Administration sBLA acceptance for first-line treatment of unresectable hepatocellular carcinoma. News release. Bristol Myers Squibb. August 21, 2024. Accessed April 4, 2025. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Receives-U.S.-Food-and-Drug-Administration-sBLA-Acceptance-for-First-Line-Treatment-of-Unresectable-Hepatocellular-Carcinoma/default.aspx
2. FDA grants priority review to Merck’s application for Welireg (belzutifan) for the treatment of patients with advanced pheochromocytoma and paraganglioma (PPGL). News release. Merck. January 27, 2025. Accessed April 4, 2025. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-welireg-belzutifan-for-the-treatment-of-patients-with-advanced-pheochromocytoma-and-paraganglioma-ppgl/
3. UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen Pharma Ltd. October 15, 2024. Accessed April 4, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-fda-acceptance-its-new-drug-application-ugn-102
4. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s supplemental biologics license application for Opdivo plus Yervoy for Patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient... News release. Bristol Myers Squibb. February 24, 2025. Accessed April 4, 2025. https://news.bms.com/news/corporate-financial/2025/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Supplemental-Biologics-License-Application-for-Opdivo-Plus-Yervoy-for-Patients-with-Unresectable-or-Metastatic-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient/default.aspx
5. FDA grants priority review to Merck’s application for KEYTRUDA® (pembrolizumab) plus standard of care as perioperative treatment for resectable locally advanced head and neck squamous cell carcinoma. News release. Merck. February 25, 2025. Accessed April 4, 2025. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-standard-of-care-as-perioperative-treatment-for-resectable-locally-advanced-head-and-neck-squamous-cel/
6. U.S. Food and Drug Administration accepts for priority review Nuvation Bio’s new drug application for taletrectinib for the treatment of advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. December 23, 2024. Accessed April 4, 2025. https://investors.nuvationbio.com/news/news-details/2024/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Nuvation-Bios-New-Drug-Application-for-Taletrectinib-for-the-Treatment-of-Advanced-ROS1-positive-Non-Small-Cell-Lung-Cancer/default.aspx
7. Verastem Oncology announces FDA acceptance and priority review of new drug application for avutometinib in combination with defactinib for the treatment of recurrent KRAS mutant low-grade serous ovarian cancer.News release. Verastem Oncology. April 4, 2025. Accessed January 2, 2025. https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-fda-acceptance-and-priority-review