Oncology Drugs Approved by the FDA in March 2025

March FDA approvals included indications for pembrolizumab plus trastuzumab, cabozantinib, and 177Lu-PSMA-617, among others.

The FDA approved several therapies in oncology in the month of March 2025. These drugs included treatments for gastrointestinal and genitourinary cancers such as prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) and advanced esophageal squamous cell carcinoma (ESCC).

Below is a full list of cancer therapeutics approved by the FDA in March.

1. Tislelizumab-jsgr with Platinum Chemotherapy for PD-L1+ Esophageal Squamous Cell Carcinoma (ESCC)

On March 4, the FDA approved the use of tislelizumab-jsgr (Tevimbra) with platinum chemotherapy as a first-line treatment for adults with PD-L1-positive, advanced ESCC, as supported by findings from the phase 3 RATIONALE-306 trial (NCT03783442).¹

The most common grade 3/4 treatment-related adverse effects (AEs; TRAEs) in the tislelizumab arm included decreased neutrophil counts (31%), decreased white blood cell counts (11%), and anemia (15%).^1,2 Six deaths in the tislelizumab arm were attributed to treatment and included GI and upper GI hemorrhage (n = 2), electrolyte imbalance (n = 1), pulmonary tuberculosis (n = 1), respiratory failure (n = 1), and myocarditis (n = 1).²

The tislelizumab combination led to a significant improvement in overall survival (OS) vs chemotherapy alone. At a median follow-up of 16.3 months (interquartile range [IQR], 8.6-21.8) in patients who received tislelizumab plus chemotherapy (n = 326) and 9.8 months (IQR, 5.8-19.0) in patients who received placebo plus chemotherapy (n = 323), the median OS was 17.2 months (95% CI, 15.8-20.1) vs 10.6 months (95% CI, 9.3-12.1), respectively (stratified HR, 0.66; 95% CI, 0.54-0.80; 1-sided P < .0001).^1,2 The 18-month OS rates in these respective arms were 48.6% (95% CI, 42.9%-54.0%) and 34.5% (95% CI, 29.2%-39.8%).²

2. Pembrolizumab Plus Trastuzumab and Chemo for HER2+, PD-L1+ Gastric/ Gastroesophageal Junction (GEJ) Adenocarcinoma

The FDA granted approval on March 19 to pembrolizumab (Keytruda) plus trastuzumab (Herceptin), fluoropyrimidine- and platinum-containing chemotherapy as a frontline treatment for adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1.³

The pembrolizumab combination’s safety profile was consistent with pembrolizumab’s known safety profile.³

The approval is based on findings from the KEYNOTE-811 trial (NCT03615326), in which pembrolizumab plus trastuzumab and chemotherapy improved OS in the intention-to-treat (ITT) population, with the most substantial benefit seen in patients whose tumors expressed PD-L1 with a combined positive score (CPS) of at least 1.³

In patients with a PD-L1 CPS of at least 1, the median progression-free survival (PFS) was 10.9 months (95% CI, 8.5-12.5) in the pembrolizumab arm vs 7.3 months (95% CI, 6.8-8.4) in the placebo arm (HR, 0.72; 95% CI, 0.60-0.87).³

3. TLX007-CDx for Prostate Cancer Imaging

On March 21, TLX007-CDx, a kit for preparing gallium-68 (⁶⁸Ga) gozetotide injection (Gozellix), received FDA approval for PSMA-PET scanning of PSMA-positive lesions in men with prostate cancer who are suspected of having metastasis and are candidates for initial definitive therapy, as well as those with suspected recurrence due to elevated serum prostate-specific antigen (PSA) levels.⁴

The novel TLX007-CDx will have a longer shelf life and wider distribution radius than previous ⁶⁸Ga gozetotide injections.¹

Approval for TLX007-CDx is based on data from the prospective, open-label PSMA-PreRP (NCT03368547 and NCT02919111) and PSMA-BCR (NCT02940262 and NCT02918357) studies, which confirmed the safety and efficacy of another formulation of ⁶⁸Ga gozetotide.^4,5

The most frequent AEs, occurring at a rate of less than 1%, were dizziness, nausea, and diarrhea.^4,5 Ascorbic acid stabilizer (Ampule), a part of the TLX007-CDx kit, contains sodium metabisulfite, which may cause reactions including life-threatening or less severe anaphylactic symptoms and asthma attacks in patients with a hypersensitivity to the sulfite.^4,5

4. Cabozantinib for Unresectable, Advanced/Metastatic Pancreatic Neuroendocrine Tumors (pNET) and Extra-Pancreatic Neuroendocrine Tumors (epNET)

Cabozantinib received FDA approval on March 26 for use in patients at least 12 years or older with unresectable, locally advanced or metastatic, well-differentiated pNETs and well-differentiated epNETs who have received prior treatment.⁶

The efficacy of cabozantinib for these indications was established by results of CABINET (NCT03375320), where, at a median follow-up of 13.9 months, patients with epNETs who received the TKI (n = 129) experienced a median PFS of 8.3 months vs 3.2 months with placebo (n = 68; stratified HR, 0.45; 95% CI, 0.30-0.66; P < .0001). At a median follow-up of 16.7 months, patients with pNETs achieved a median PFS of 11.4 months vs 3.0 months in the cabozantinib (n = 62) and placebo (n = 31) arms, respectively (stratified HR, 0.27; 95% CI, 0.14-0.49; P < .0001), according to findings presented at the 2023 European Society for Medical Oncology (ESMO) Congress.⁷

For patients in the pNETs cohort, which was randomized 2:1 for patients to receive 60 mg of cabozantinib orally once daily or placebo until disease progression or unacceptable toxicity, median PFS was 13.8 months (95% CI, 8.9-17.0) in the cabozantinib arm and 3.3 months (95% CI, 2.8-5.7) in the placebo arm (hazard ratio [HR], 0.22; 95% CI, 0.12-0.41; P <0.0001). Likewise, objective response rate (ORR) was 18% (95% CI, 10%-30%) and 0% (95% CI, 0%-11%) in the respective arms.⁶

Safety was consistent with the approved product label.

5. 177Lu-PSMA-617 for PSMA+ Metastatic Castration-Resistant Prostate Cancer (mCRPC)

On March 28, the FDA expanded the label of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617; Pluvicto) to include indications for PSMA-positive mCRPC in adults who have previously received androgen receptor pathway inhibitor (ARPI) therapy and are appropriate candidates to delay taxane-based chemotherapy.⁷

AEs were consistent with previous known experience with the drug; use of lutetium Lu 177 vipivotide tetraxetan may lead to risk from radiation exposure, myelosuppression, and renal toxicity.⁷

The efficacy of 177Lu-PSMA-617 was evaluated in the randomized, multicenter, open-label trial PSMAfore (NCT04689828), where radiographic progression-free survival (rPFS) and OS were the primary and secondary end points, respectively. Median rPFS was 9.3 months (95% CI, 7-not estimable [NE]) for patients on the experimental drug and 5.6 months (95% CI, 4-6) for patients taking another ARPI (hazard ratio [HR], 0.41; 95% CI, 0.29-0.56; P < .0001).⁷

Median OS for the experimental arm was 24.5 months (95% CI, 19.5-28.9) and 23.1 months (95% CI, 19.6-25.5; HR, 0.91; 95% CI, 0.72-1.14; P-value not statistically significant), respectively.⁷

6. Perioperative Durvalumab Plus Chemotherapy for Muscle Invasive Bladder Cancer (MIBC)

The FDA approved neoadjuvant therapy with durvalumab (Imfinzi) for use with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy after radical cystectomy in adults with MIBC.⁸

The combination’s efficacy was shown in the randomized, open-label, multicenter phase 3 trial NIAGARA (NCT03732677), in which 1,063 patients were randomized 1:1 to treatment with neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery.⁸

Median event-free survival (EFS) was not reached (NR) in the durvalumab plus chemotherapy arm (95% CI, NR-NR) vs 46.1 months (95% CI, 32.2-NR) in the chemotherapy arm (hazard ratio [HR], 0.68; 95% CI, 0.56-0.82; two-sided P < .0001). Median OS was NR in both arms (HR, 0.75; 95% CI, 0.59-0.93; two-sided P = .0106).⁸

Previously reported results from a pre-planned interim analysis of NIAGARA that compared the above treatment with durvalumab and chemotherapy to placebo indicated that the combination indicated no new safety signals.

The most common any-grade AEs were nausea (durvalumab arm, 54%; placebo arm, 49%), anemia (39%; 41%), constipation (39%; 39%), fatigue (36%; 32%), urinary tract infection (30%; 29%), decreased appetite (27%; 25%), neutropenia (26%; 31%), pyrexia (21%; 17%), diarrhea (21%; 14%), vomiting (19%; 18%), blood creatinine increase (19%; 15%), asthenia (18%; 18%), neutrophil count decrease (15%; 14%), and pruritis (15%; 7%).⁹

Reference

1. Tevimbra approved in US for first-line treatment of advanced esophageal squamous cell carcinoma in combination with chemotherapy. News release. BeiGene, Ltd. March 4, 2025. Accessed March 4, 2025. https://hkexir.beigene.com/news/tevimbra-approved-in-u-s-for-first-line-treatment-of-advanced-esophageal-squamous-cell-carcinoma-in-combination/8379a7c3-35ce-45af-82d3-164c64ecf37c/
2. Xu J, Kato K, Raymond E, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24(5):483-495. doi:10.1016/S1470-2045(23)00108-0
3. FDA. FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). March 19, 2025. Accessed March 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma
4. FDA approves new prostate cancer imaging agent Gozellix. News release. Telix Pharmaceuticals. Published online March 21, 2025. Accessed March 21, 2025. https://www.globenewswire.com/news-release/2025/03/21/3046974/0/en/FDA-Approves-New-Prostate-Cancer-Imaging-Agent-Gozellix.html
5. Gozellix. Prescribing information. Telix Pharmaceuticals. 2025. Accessed March 21, 2025. https://telixpharma.com/wp-content/uploads/2025/03/Gozellix-prescribing-information.pdf
6. FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. FDA. March 26, 2025. Accessed March 26, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet?utm_medium=email&utm_source=govdelivery
7. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
8. FDA approves durvalumab for muscle invasive bladder cancer. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer
9. Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5