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

FDA Approval Roundup

Below is your guide to all the oncologic therapeutic options cleared by the FDA in March 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.

3/4: Frontline Tislelizumab Plus Chemotherapy in Unresectable or Metastatic ESCC

The regulatory agency cleared tislelizumab-jsgr (Tevimbra), the humanized IgG4 anti–PD-1 monoclonal antibody, in combination with platinum-containing chemotherapy as a first-line regimen for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) with a tumor PD-L1 tumor area positivity (TAP) of 1% or higher. In this subset, the tislelizumab regimen (n = 231) led to a median overall survival (OS) of 16.8 months (95% CI, 15.3-20.8) vs 9.6 months (95% CI, 8.9-11.8) with chemotherapy alone (n = 250; HR, 0.66; 95% CI, 0.53-0.82), according to data from the phase 3 RATIONALE-306 trial (NCT03783442).

“We should be able to easily incorporate this [regimen] into our treatment paradigms,” Nataliya Uboha, MD, PhD, said in an interview with OncLive®. “Tislelizumab can be combined with different chemotherapy backbones and should be built into treatment guidelines for patients with ESCC.” Uboha is a faculty leader for the Early Phase Oncology Therapeutics Program at the University of Wisconsin Carbone Cancer Center, as well as an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health in Madison.

OTHER RELATED COVERAGE

Sunnie Kim, MD

• In a recent OncLive On Air episode, Uboha delved in the significance of the approval, highlighted key efficacy and safety data from RATIONALE-306, and shared considerations for integrating this agent into the ESCC treatment paradigm.
• Recent data from a post hoc analysis of the study were shared during the 2025 Gastrointestinal Cancers Symposium and showed that among patients with locally advanced unresectable or metastatic ESCC who responded to frontline tislelizumab plus chemotherapy, deeper responses and a longer time to maximum response were linked with prolonged OS.
• In a past interview, Sunnie Kim, MD, assistant professor, medicine — medical oncology, University of Colorado Anschutz Medical Campus, contextualized the use of tislelizumab as a frontline treatment option in advanced ESCC.
• In a past OncLive News Network, Harry H. Yoon, MD, and Nabil F. Saba, MD, FACP, further discussed tislelizumab and its investigation in the RATIONALE-306 study.

3/19: Pembrolizumab Plus Trastuzumab/Chemo in PD-L1+, HER2+ Gastric/GEJ Adenocarcinoma

Pembrolizumab (Keytruda) paired with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy received traditional approval from the FDA for first-line use in adult patients with locally advanced or unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors had a PD-L1 combined positive score of at least 1. The full approval was based on data from the phase 3 KEYNOTE-811 trial (NCT03615326).

Yelena Y. Janjigian, MD

In this subset, the pembrolizumab regimen (n = 298) led to a median OS of 20.1 months (95% CI, 17.9-22.9) vs 15.7 months (95% CI, 13.5-18.5) with trastuzumab/chemotherapy alone (n = 296; HR, 0.79; 95% CI, 0.66-0.95). In the respective arms, the median progression-free survival was 10.9 months (95% CI, 8.5-12.5) and 7.3 months (95% CI, 6.8-8.4), respectively (HR, 0.72; 95% CI, 0.60-0.87). The respective overall response rates were 73% (95% CI, 68%-78%) and 58% (95% CI, 53%-64%).

In a past interview, Yelena Y. Janjigian, MD, chief of Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, shed light on the results from the final OS analysis of KEYNOTE-811.

OTHER RELATED COVERAGE

• After the regimen received accelerated approval in May 2021, in November 2023, the regulatory agency restricted the indication just to include those with a PD-L1 CPS of 1 or more per an FDA-approved test. In the same month, the FDA cleared the PD-L1 IHC 22C3 pharmDx diagnostic tool to aid in the identification of eligible candidates for the combination regimen.
• In a recent OncLive News Network, Mohammed Najeeb Al Hallak, MD, MS, of Karmanos Cancer Institute, and Sakti Chakrabarti, MD, of Case Western Reserve University, shed light on the final OS data from KEYNOTE-811 and what it means for clinical practice.

3/26: Cabozantinib in Pancreatic and Extrapancreatic Neuroendocrine Tumors

Cabozantinib (Cabometyx) won approval from the FDA for use in adult and pediatric patients aged 12 years and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic and extrapancreatic neuroendocrine tumors (pNET; epNET)—making it the first and only systemic therapy cleared for previously treated NETs irrespective of primary tumor site, grade, somatostatin receptor expression, and functional status. The decision was supported by findings from 2 cohorts of the phase 3 CABINET trial (NCT03375320).

In the pNET cohort (n = 99), the median PFS with cabozantinib (n = 66) was 13.8 months (95% CI, 8.9-17.0) vs 3.3 months (95% CI, 2.8-5.7) with placebo (n= 33; HR, 0.22; 95% CI, 0.12-0.41; P < .0001). The ORRs in the respective arms were 18% (95% CI, 10%-30%) and 0% (95% CI, 0%-11%). In the epNET cohort (n = 199), the median PFS with the agent (n = 132) was 8.5 months (95% CI, 6.8-12.5) vs 4.2 months (95% CI, 3.0-5.7) with placebo (n = 67; HR, 0.40; 95% CI, 0.26-0.61; P < .0001). The ORRs in the respective arms were 5% (95% CI, 2.2%-11%) and 0% (95% CI, 0%-5%).

“This approval really means that we have a new standard option to offer to patients with neuroendocrine tumors who've had at least 1 other line of therapy and whose disease is progressing and needs additional therapy to control growth,” said Jennifer Chan, MD, MPH, in an exclusive interview. Chan is an associate professor of medicine at Harvard Medical School and clinical director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute.

OTHER RELATED COVERAGE

• In a recent interview, Jonathan R. Strosberg, MD, of Moffitt Cancer Center, discussed findings from a subgroup analysis of CABINET presented during the 2025 Gastrointestinal Cancers Symposium. “When considering similar drugs [to cabozantinib] in this space, everolimus [Afinitor], is strictly approved for non-hormonally functional NETs, a category that excludes many GI primaries, which are hormone-producing, functional tumors,” he said. “In [the CABINET] study, however, no distinction was observed between functional and nonfunctional tumors or between small bowel/midgut and non-midgut tumors. The benefit of treatment was seen consistently across the population.”
• In a past Insights program, Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, reflected on the role of VEGF therapies like cabozantinib in the treatment of patients with NETs.

3/28: Perioperative Durvalumab Plus Chemo in Muscle-Invasive Bladder Cancer

Data from the phase 3 NIAGARA trial (NCT03732677) supported the FDA’s decision to approve durvalumab (Imfinzi) paired with gemcitabine and cisplatin as neoadjuvant treatment, followed by durvalumab monotherapy as adjuvant treatment following radical cystectomy, for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

The event-free survival in the durvalumab arm (n = 533) was not reached (NR; 95% CI, NR-NR) vs 46.1 months (95% CI, 32.2-NR) in the gemcitabine/cisplatin–alone arm (n = 530; HR, 0.68; 95% CI, 0.56-0.82; 2-sided P < .0001). The median OS in the respective arms was NR (HR, 0.75; 95% CI, 0.59-0.93; 2-sided P = .0106).

“The significance of the approval of perioperative durvalumab for the treatment of patients with MIBC is that it really represents the first time that a treatment has been added to standard cisplatin-based chemotherapy in the neoadjuvant setting, which has improved outcomes,” Matthew Galsky, MD, said in an exclusive interview. Galsky is a professor of medicine (hematology and medical oncology) and urology at the Icahn School of Medicine at Mount Sinai. He is also the director of genitourinary medical oncology co-director of the Center of Excellence for Bladder Cancer and associate director for Translational Research at The Tisch Cancer Institute.

OTHER RELATED COVERAGE

Guru P. Sonpavde, MD

• In a recent episode of MedNews Week’s Oncology Unplugged, Chandler Park, MD, of Norton Cancer Institute, sat down with Petros Grivas, MD, PhD, of Fred Hutchinson Cancer Center and University of Washington School of Medicine, shared key updates from the 2025 Genitourinary Cancers Symposium, including data from NIAGRA and how they may represent a paradigm shift in perioperative management.
• In a past interview, Guru P. Sonpavde, MD, of AdventHealth Cancer Institute, discussed the implications of treatment with the NIAGARA regimen in cisplatin-eligible patients with MIBC.

3/28: Lutetium Lu 177 Vipivotide Tetraxetan in PSMA+ Metastatic Castration-Resistant Prostate Cancer

The regulatory agency expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibitor therapy and are eligible to delay taxane-based chemotherapy.

The decision was based on findings from the phase PSMAfore study (NCT04689828). In this population, the median radiographic PFS with lutetium Lu 177 vipivotide tetraxetan (n = 234) was 9.3 months (95% CI, 7-not estimable) vs 5.6 months (95% CI, 4-6) in those who switched to a different AR pathway inhibitor (n = 234; HR, 0.41; 95% CI, 0.29-0.56; P < .0001).

“The FDA’s expanded approval of [lutetium Lu 177 vipivotide tetraxetan] marks a transformative step forward in the treatment of mCRPC, underscoring the growing impact of precision oncology,” Jorge A. Garcia, MD, a genitourinary medical oncologist and chair of the Solid Tumor Oncology Division at University Hospitals Seidman Cancer Center/Case Western Reserve University in Cleveland, Ohio, told OncLive®. “By enabling access to this targeted radioligand therapy prior to chemotherapy, we are not only broadening treatment options but also redefining the standard of care for PSMA-positive disease.”

Additionally, in a recent interview, Michael J. Morris, MD, a medical oncologist and head of the Prostate Cancer Section at Memorial Sloan Kettering Cancer Center, further discussed the significance of the approval:

OTHER RELATED COVERAGE

Chandler Park, MD

• In a recent interview, Oliver Sartor, MD, of Mayo Clinic, delved into data from the second interim analysis of PSMAfore, underscoring that the findings underscore the favorable safety and efficacy profile of the drug across a spectrum of clinical end points.
• In a past interview, Chandler Park, MD, of Norton Cancer Institute, shed light on the emerging field of radiotheragnostics and the increasing utilization of biomarker testing in prostate cancer, touching on PSMAfore and how that fits into the mix.
• In another past interview, Praful K. Ravi, MD, BChir, MRCP, of Dana-Farber Cancer Institute and Harvard Medical School, detailed clinical trials investigating the use of PSMA-targeted therapies in mCRPC.

Other Noteworthy Decisions:

1. The next-generation PET imaging agent TLX007-CDx, a kit for the preparation of gallium-68 gozetotide injection (Gozellix) was cleared for use in PET scanning of prostate-specific membrane antigen–positive lesions in men with prostate cancer who have suspected metastasis and are candidates for initial definitive therapy, and those with suspected recurrence based on elevated serum prostate-specific antigen level.
2. The regulatory agency gave the green light to the biosimilars denosumab-bmwo (Stobloco) and (Osenvelt), referencing denosumab (Prolia) and (Xgeva), respectively, for use in all indications of the reference products, expanding options for osteoporosis and cancer-related bone conditions.

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