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

OncLive's FDA Approval Roundup

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

4/8: Nivolumab Plus Ipilimumab in dMMR/MSI-H Metastatic CRC

Indication: Over 2 months ahead of the Prescription Drug Use Fee Act goal date, the regulatory agency cleared the immunotherapy doublet comprised of nivolumab (Opdivo) and ipilimumab (Yervoy) for use in adult and pediatric patients aged 12 years or older with mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) unresectable or metastatic colorectal cancer (CRC) based on findings from the phase 3 CheckMate 8HW trial (NCT04008030).

Supporting Data: The first-line combination (n = 171) led to a 79% reduction in the risk of disease progression or death vs chemotherapy (n = 84; HR, 0.21; 95% CI, 0.14-0.32; P < .0001). The median progression-free survival (PFS) in the immunotherapy arm was not reached (NR; 95% CI, 38.4-not evaluable [NE]) vs 5.8 months (95% CI, 4.4-7.8) in the chemotherapy arm. Additionally, across all lines, nivolumab plus ipilimumab (n = 296) led to a 38% reduction in the risk of death vs nivolumab alone (n = 286; HR, 0.62; 95% CI, 0.48-0.81; P = .0003). The median PFS was NR (95% CI, 53.8-NE) with the doublet vs 39.3 months (95% CI, 22.1-NE) with the monotherapy.

Heinz-Josef Lenz, MD

Significance: According to Bristol Myers Squibb, nivolumab plus ipilimumab represents the first-ever dual immune checkpoint inhibitor regimen to showcase significant efficacy benefit vs single-agent nivolumab and chemotherapy in this subset of patients.

“I encourage [all oncologists] to try [to use this combination in practice] because it is by far the most effective treatment for this patient population,” Heinz-Josef Lenz, MD, of Keck School of Medicine of the University of Southern California, said in an exclusive interview with OncLive®.

OncLive also spoke with Van Karlyle Morris, MD, of The University of Texas MD Anderson Cancer Center in Houston, about the significance of the approval:

OTHER RELATED COVERAGE

• In a combined QA, Lenz and Morris further discuss the FDA decision, the evolution of data from CheckMate 8HW, and how the availability of the combination offers an additional option for individualized CRC treatment considerations.

Tanios S. Bekaii-Saab, MD, FACP

• In an earlier interview, Thierry Andrè, MD, of Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris, discussed earlier CheckMate 8HW data released during the 2025 Gastrointestinal Cancers Symposium.
• Earlier this year, in February 2025, Lenz also hosted a Rapid Readout program in which he walked through the first results from CheckMate 8HW.
• Tanios S. Bekaii-Saab, MD, FACP, of Mayo Clinic, hosted another Rapid Readout on the trial in January 2025.

ALSO APPROVED: The FDA also converted the accelerated approval of single-agent nivolumab to a full approval for use in adult and pediatric patients aged 12 years or older with MSI-H or dMMR metastatic CRC who have progressed following fluoropyrimidine, oxaliplatin, and irinotecan.

4/10: Larotrectinib in NTRK+ Solid Tumors

Indication: A couple of days later, the regulatory agency granted traditional approval to larotrectinib (Vitrakvi) for use in adult and pediatric patients with solid tumors harboring an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to lead to severe morbidity and have no satisfactory alternative options or that have progressed after treatment. The agent previously received accelerated approval in November 2018, representing the second tissue-agnostic approval in cancer treatment.

Supporting Data: The decision was based on findings from the following multicenter, open-label, single-arm trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431). Pooled data indicated that the agent (n = 339) elicited an objective response rate (ORR) of 60% (95% CI, 55%-65%), with a complete response rate of 24% and a partial response rate of 36%. The median duration of response (DOR) was 43.3 months (95% CI, 32.5-NE). Notably, 64% of patients continued to respond to treatment for longer than 12 months, and 45% did so for longer than 24 months.

Significance: “The full approval of Vitrakvi by the FDA is a welcome step forward, solidifying its place as a treatment option for patients with NTRK gene fusion–positive cancers,” Andrea Ferris, president and chief executive officer of LUNGevity Foundation, stated in a news release. “This milestone not only benefits patients today but also paves the way for further advancements in NTRK gene therapies in the future.”

OTHER RELATED COVERAGE

• Earlier data from NAVIGATE shared during the 2024 Gastrointestinal Cancer Symposium indicated that larotrectinib led to durable responses, favorable survival, and an acceptable safety profile in patients with TRK fusion–positive gastrointestinal cancers.

Benjamin Levy, MD

• Previously, in 2022, Benjamin Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, led a Rapid Readout program in which he detailed safety and efficacy results of larotrectinib in patients with TRK fusion–positive lung cancer.
• In the same year, Maria E. Cabanillas, MD, of The University of Texas MD Anderson Cancer Center, also hosted a Rapid Readout, which delved into the safety and efficacy of larotrectinib in patients with advanced TRK fusion–positive thyroid carcinoma.
• Findings from a matching-adjusted indirect comparison of real-world data shared during the 2022 ASCO Annual Meeting indicated that treatment with larotrectinib prolonged overall survival vs standard-of-care therapy in patients with TRK fusion–positive cancer.
• David A. Reardon, MD, of Dana-Farber Cancer Institute, previously hosted a Rapid Readout in 2021 in which he walked through data from NAVIGATE and SCOUT shared during that year’s ASCO Annual Meeting.

4/11: Nivolumab Plus Ipilimumab in Unresectable or Metastatic HCC

Indication and Supporting Data: The FDA also cleared nivolumab plus ipilimumab for frontline use in adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) based on data from the phase 3 CheckMate 9DW trial (NCT04039607). Here, the doublet (n = 335) led to a 21% reduction in the risk of death vs investigator’s choice of lenvatinib (Lenvima) or sorafenib (Nexavar; n = 333; HR, 0.79; 95% CI, 0.65-0.96; P = .0180). The median overall survival was 23.7 months (95% CI, 18.8-29.4) with the immunotherapy combination vs 20.6 months (95% CI, 17.5-22.5) with lenvatinib or sorafenib.

Moreover, the respective ORRs achieved with the doublet and lenvatinib or sorafenib at 36.1% (95% CI, 31.0%-41.5%) and 13.2% (95% CI, 9.8%-17.3%), respectively (P < .0001). The median DOR with dual immunotherapy was 30.4 months (95% CI, 21.2-not reached) vs 12.9 months (95% CI, 10.2-31.2) with investigator’s choice of treatment.

Significance: “[The CheckMate 9DW trial is] a global study with the best median OS [we have seen] so far, as well as the highest ORR in a global phase 3 study [in this population],” Ruth He, MD, PhD, of MedStar Health Lombardi Cancer Center, said in an interview with OncLive. “What is also amazing is that [with nivolumab plus ipilimumab], now we are reaching 2 years of [median] OS [duration], the ORR is 36%, and the [median] DOR is also amazing, at 30.4 months. This is an effective regimen, and it adds to the treatment options for patients with this disease.”

OTHER RELATED COVERAGE

Amit Singal, MD, MS

• Panelists of a prior Peer Exchange walked through key updates from the 2024 ASCO Annual Meeting and the 2024 ESMO Congress, including results from the CheckMate 9DW trial of ipilimumab plus nivolumab in first- and second-line treatment.
• In a past Insights program, Amit Singal, MD, MS, of UT Southwestern Medical Center, and Stephen L. Chan, MD, of Chinese University of Hong Kong, review first-line trials for unresectable HCC.

4/24: Penpulimab in Non-Keratinizing Nasopharyngeal Carcinoma

Indication: The regulatory agency greenlit penpulimab-kcqx plus cisplatin or carboplatin and gemcitabine for the frontline treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC), and as a monotherapy for adult patients with metastatic non-keratinizing NPC with disease progression on or following platinum-based chemotherapy and at least 1 other previous line of therapy.

Supportive Data: The respective decisions were based on findings from the phase 3 Study AK105-304 (NCT049743980) and phase 2 Study AK105-202 (NCT03866967). Findings from the former study showed that penpulimab plus chemotherapy (n = 144) led to a median PFS of 9.6 months (95% CI, 7.1-12.5) vs 7.0 months (95% CI, 6.9-7.3) with chemotherapy (n = 147; HR, 0.45; 95% CI, 0.33-0.62; P < .0001). Data from the latter study indicated that penpulimab (n = 125) elicited an ORR of 28% (95% CI, 20%-37%) and a median DOR that was NR (95% CI, 9.2-NE). Notably, 46% of patients continued to respond for at least 12 months.

Significance: “This milestone enhances international treatment guidelines for advanced NPC and extends the benefits of China’s innovations to global patients, ultimately reshaping the treatment landscape for metastatic NPC worldwide,” Prof. Chaosu Hu, of Fudan University Shanghai Cancer Center, stated in a news release.

OTHER RELATED COVERAGE

• Data from Study AK105-304 were shared during the 2025 AACR Annual Meeting.
• In March 2025, the National Medical Products Administration approved penpulimab plus chemotherapy for first-line use in patients with recurrent or metastatic NPC.

Other Noteworthy Decisions:

The FDA has approved a ready-to-dilute formulation of thiotepa (Tepylute) in a 100-mg/10-mL multidose vial for the treatment of patients with breast and ovarian cancer.