Spotlighting the Top 10 FDA Oncology Approvals in 2025

Given the robust year for the FDA and clinical developments in oncology as a whole, here are 10 of the top approvals CancerNetwork® covered in the year 2025.

Regarding the field of oncology, 2025 was a busy year for the FDA. The agency, which regulates drugs and products intended for human use while assessing their relative benefit prior to granting marketing authorization for interstate commerce, granted dozens of approvals to drugs and products across a variety of modalities and a multitude of disease states in oncology care.1

Given the robust year for the FDA and clinical developments in oncology as a whole, here are 10 of the top approvals CancerNetwork® covered in the year 2025.

#1: FDA Approves Sotorasib/Panitumumab in KRAS G12C-Mutated CRC

Based on data from the phase 3 CodeBreaK 300 trial (NCT05198934), the FDA approved sotorasib (Lumakras) plus panitumumab (Vectibix) among patients with KRAS G12C-mutated metastatic colorectal cancer (CRC) who previously received therapy containing fluoropyrimidine, oxaliplatin, or irinotecan.2 Patients were randomly assigned 1:1:1 to receive sotorasib at 960 mg orally once daily plus panitumumab at 6 mg/kg intravenously every 2 weeks, sotorasib at 240 mg orally once daily plus panitumumab at 6 mg/kg intravenously every 2 weeks, or investigator’s choice of standard-of-care (SOC) therapy.3 In addition, the FDA approved the therascreen KRAS RGQ PCR Kit, a companion diagnostic device to help to identify patients with CRC who have tumors that harbor a KRAS G12C mutation.

Efficacy data showed that among patients treated with 960 mg of sotorasib and 6 mg/kg of panitumumab, the median progression-free survival (PFS) was 5.6 months (95% CI, 4.2-6.3) vs 2.0 months (95% CI, 1.9-3.9) among patients treated with SOC therapy (HR, 0.48; 95% CI, 0.30-0.78; P = .005). The final overall survival (OS) data were not significant; however, an overall response rate (ORR) of 26% (95% CI, 15%-40%) vs 0% (95% CI, 0%-7%) was observed in the investigational and SOC arms, respectively.

#2: FDA OKs Leuprolide Mesylate 3-Month Formulation in Advanced Prostate Cancer

The FDA approved a 3-month acting injectable formulation of leuprolide mesylate (Camcevi) among patients with advanced prostate cancer based on results from the phase 3 FP-001 LMIS trial (NCT03261999).4-6 Patients (n = 144) in the trial received 1 or 2 doses of the drug, of which 132 received 2.

Data from the trial revealed 97.9% of patients achieved a serum testosterone concentration suppression to castrate levels from days 28 to 168, with a mean testosterone concentration of 17.8 ng/dL and a suppression rate of 98.6%. No increase in testosterone was observed at the time of second injection, and 3 patients did not experience suppression of testosterone by the primary efficacy end point analysis.

#3: FDA Approves T-DXd in HER2-Low/Ultralow Breast Cancer

Trastuzumab deruxtecan (T-DXd; Enhertu) received FDA approval as a treatment for patients with unresectable or metastatic HER2-low or HER2-ultralow breast cancer who previously received at least 1 line of endocrine therapy in the metastatic setting.7 The regulatory decision was supported by findings from the phase 3 DESTINY-Breast06 trial (NCT04494425), wherein T-DXd was assessed against investigator’s choice of chemotherapy in patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow advanced or metastatic breast cancer.

Findings presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting revealed a median PFS of 13.2 months with T-DXd vs 8.1 months with chemotherapy in the HER2-low group (HR, 0.62; 95% CI, 0.51-0.74; P <.0001), 13.2 months vs 8.3 months in the HER2-ultralow group (HR, 0.78; 95% CI, 0.50-1.21), and 13.2 months vs 8.1 months, respectively, in the intent-to-treat (ITT) group (HR, 0.63; 95% CI, 0.53-0.75; P <.0001).8 The confirmed ORR in the respective groups was 56.5% vs 32.2%, 61.8% vs 26.3%, and 57.3% vs 31.2%, respectively.

#4: Zongertinib Earns FDA Accelerated Approval in HER2+ NSCLC

The FDA granted accelerated approval to zongertinib (Hernexeos) for the treatment of adults with nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) activating mutations previously treated for metastatic or unresectable disease.9 Additionally, the agency approved the Oncomine Dx Target Test as a companion diagnostic for identifying HER2 TKD activating mutations among those potentially eligible to receive zongertinib. Forming the basis for the regulatory decision was the phase 1b Beamion LUNG-1 trial (NCT04886804), which assessed zongertinib in 71 patients who received prior platinum-containing chemotherapy.

Among patients who did not receive prior anti-HER2 tyrosine kinase inhibitors or antibody drug conjugates (ADCs), the ORR was 75% (95% CI, 63%-83%), and 58% experienced a response lasting at least 6 months. Among those who received a prior HER2-directed ADC, the ORR was 44% (95% CI, 29%-61%), and 27% experienced a response for at least 6 months. The recommended dose was dependent on body weight, with patients weighing less than 90 kg recommended for 120 mg once daily and those at 90 kg or higher recommended for 180 mg once daily.

#5: FDA Approves Perioperative Pembrolizumab Plus Radiation in HNSCC

Based on results from the phase 3 KEYNOTE-689 trial (NCT03765918), the FDA approved neoadjuvant pembrolizumab (Keytruda) monotherapy plus adjuvant pembrolizumab and radiotherapy with or without cisplatin after surgery and then pembrolizumab monotherapy among patients with PD-L1–positive locally advanced head and neck squamous cell carcinoma (HNSCC).10 In the trial, patients were randomly assigned to receive adjuvant radiotherapy with or without cisplatin alone with or without pembrolizumab.

In the pembrolizumab and comparator arms, the median event-free survival (EFS) was 59.7 months (95% CI, 37.9-not reached [NR]) vs 29.6 months (95% CI, 19.5-41.9), respectively (HR, 0.70; 95% CI, 0.55-0.89; P = .00140). Moreover, the pembrolizumab-based regimen did not trend toward detrimental outcomes after accounting for 76% of pre-specified deaths in the PD-L1–positive group. The agent was approved at 200 mg every 3 weeks or 400 mg every 6 weeks prior to chemotherapy when administered on the same day.

#6: FDA Approves Zanubrutinib Tablets in Multiple Hematologic Indications

A tablet formulation of zanubrutinib (Brukinsa) was approved across 5 hematologic indications, including chronic lymphocytic leukemia or small lymphocytic lymphoma; Waldenström macroglobulinemia; pretreated mantle cell lymphoma (MCL); relapsed/refractory marginal zone lymphoma following at least 1 CD20-based regimen; and with obinutuzumab (Gazyva) in relapsed/refractory follicular lymphoma following at least 2 lines of systemic therapy.11 The regulatory decision was supported by findings from 2 phase 1 crossover studies, which showed that the tablet formulation exhibited comparable efficacy and safety outcomes to capsules.

The recommended dose of zanubrutinib is 320 mg orally; the tablets contain 160 mg each compared with 80 mg in each capsule, requiring ingestion of 2 tablets vs 4 capsules. In addition, the tablets are smaller and have a film coating, enhancing the ease of swallowing for patients.

#7: FDA Approves PET Imaging Agent for Prostate Cancer

TXL007-CDx (Gozellix), a kit used for the preparation of gallium-68 gozetotide (68Ga) injection, received FDA approval for use in patients with prostate cancer.12 The kit is indicated for PET scanning for prostate-specific membrane antigen (PSMA) following 68Ga radiolabeling among patients with prostate cancer with suspected metastasis who may be candidates for definitive therapy; patients may be eligible to receive this treatment if a suspicion of recurrence arises based on the elevated serum prostate-specific antigen level.

Results from the PSMA-PreRP (NCT03368547 and NCT02919111) and PSMA-BCR trials (NCT02940262 and NCT02918357) supported the approval.13 Each trial evaluated different formulations of 68Ga gozetotide.

#8: FDA Approves Acalabrutinib Combo in Previously Untreated MCL

The addition of acalabrutinib (Calquence) to bendamustine (Treanda) and rituximab (Rituxan) received FDA approval as a treatment for patients with previously untreated MCL ineligible to receive autologous hematopoietic stem cell transplantation.14 Findings from the phase 3 ECHO trial (NCT02972840) supported the FDA decision; therein, patients received the acalabrutinib-based regimen or placebo plus bendamustine and rituximab.15

The median PFS in the acalabrutinib vs SOC groups was 66.4 months vs 49.6 months, and the risk of disease progression or death was 27% lower for the acalabrutinib group (HR, 0.73; 95% CI, 0.57-0.94; P = .016). Moreover, the OS favored patients treated with the acalabrutinib-based regimen (HR, 0.86; 95% CI, 0.65-1.13; P = .2743), and data were immature at the time of the analysis.

#9: FDA Approves Radioligand Therapy in PSMA–Positive, Castration-Resistant PC

The FDA expanded the indication of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adults with PSMA-positive, metastatic castration-resistant prostate cancer (CRPC) previously treated with androgen receptor pathway inhibitor (ARPI) therapy deemed appropriate to delay taxane-based therapy.16 Data supporting the regulatory decision came from the phase 3 PSMAfore trial (NCT04689828), which randomly assigned patients 1:1 to receive lutetium Lu 177 vipivotide tetraxetan or a different ARPI.

In the experimental and ARPI cohorts, the median radiographic PFS was 9.3 months (95% CI, 7-not estimable [NE]) and 5.6 months (95% CI, 4-6), respectively (HR, 0.41; 95% CI, 0.29-0.56; P <.0001). The median OS was 24.5 months (95% CI, 19.5-28.9) vs 23.1 months (95% CI, 19.6-25.5) in each arm (HR, 0.91; 95% CI, 0.72-1.14), and 60% of patients initially assigned to ARPIs switched to receive lutetium Lu 177 vipivotide tetraxetan following disease progression.

#10: FDA Approves Belzutifan in Adult/Pediatric Pheochromocytoma and Paraganglioma

The FDA granted approval to belzutifan (Welireg), an oral HIF-2α inhibitor, as a treatment in patients 12 years and older with advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).17 Support for the decision was derived from findings from the phase 2 LITESPARK-015 trial (NCT04924075), which assessed 120 mg of oral belzutifan in this patient population.18

Among all patients, the ORR was 26% (95% CI, 17%-38%), and the median duration of response was 20.4 months (95% CI, 8.3-NR). A total of 32% (95% CI, 20%-45%) of patients had a reduction in antihypertensive medications by at least 50% for a minimum of 6 months. The ORR in patients with renal cell carcinoma was 83% (95% CI, 59%-96%); in those with solid central (CNS) nervous system hemangioblastomas, it was 100% (95% CI, 59%-100%); in solid and cystic CNS hemangioblastoma, it was 60% (95% CI, 26%-88%); and in pancreatic neuroendocrine tumors, it was 67% (95% CI, 35%-90%).

References

1. Is it really ‘FDA Approved’? FDA. Accessed December 22, 2025. https://www.fda.gov/consumers/consumer-updates/it-really-fda-approved
2. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed December 22, 2025. https://shorturl.at/1WviB
3. Fakih M, Salvatore L, Esaki T, et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC). J Clin Oncol. 2024;42(17). doi:10.1200/JCO.2024.42.17_suppl.LBA3510
4. Foresee Pharmaceuticals announces FDA approval of CAMCEVI ETM for the treatment of advanced prostate cancer. News release. Foresee Pharmaceuticals. August 28, 2025. December 22, 2025. https://tinyurl.com/mrtx3xsn
5. Foresee Pharmaceuticals announces the PDUFA goal date for the 3-month version of CAMCEVI is August 29, 2025. News release. Foresee Pharmaceuticals. January 13, 2025. Accessed December 22, 2025. https://tinyurl.com/4fbd82d5
6. Foresee Pharmaceuticals announces successful topline results from phase 3 registration study of LMIS 25 mg in prostate cancer. News release. Foresee Pharmaceuticals. February 21, 2019. Accessed December 22, 2025. https://tinyurl.com/6x3yy2pv
7. Enhertu approved in the US as first HER2-directed therapy for patients with HER2-low or HER2-ultralow metastatic breast cancer following disease progression after one or more endocrine therapies. News release. FDA. January 27, 2025. Accessed December 22, 2025. https://tinyurl.com/5n8ab8sk
8. Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). J Clin Oncol. 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000
9. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. FDA. August 8, 2025. Accessed December 22, 2025. https://tinyurl.com/bdh2d4uc
10. FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma. News release. FDA. June 12, 2025. Accessed December 22, 2025. https://tinyurl.com/yt9p66xz
11. U.S. FDA approves tablet formulation of BeOne’s BRUKINSA® for all approved indications. News release. BeOne Medicines, Ltd. June 11, 2025. Accessed December 22, 2025. https://tinyurl.com/3a42b49a
12. FDA approves new prostate cancer imaging agent Gozellix. News release. Telix. March 20, 2025. Accessed December 22, 2025. https://tinyurl.com/kexv2u7e
13. Gozellix. Prescribing Information. Telix. March 2025. Accessed December 22, 2025. https://tinyurl.com/3ekajmp9
14. FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. January 16, 2025. Accessed December 22, 2025. https://shorturl.at/fTW0O
15. Calquence combination regimen demonstrated statistically significant and clinically meaningful improvement in progression-free survival in 1st-line mantle cell lymphoma in ECHO phase III trial. News release. AstraZeneca. May 2, 2024. December 22, 2025. https://tinyurl.com/py9tdkp6
16. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed December 22, 2025. https://tinyurl.com/y77tmenc
17. FDA approves belzutifan for pheochromocytoma or paraganglioma. News release. FDA. May 14, 2025. Accessed December 22, 2025. https://tinyurl.com/2j5eetc6
18. Qiu J, Zhou J, Cai L, et al. Belzutifan monotherapy in Chinese patients (pts) with von Hippel-Lindau (VHL) disease–associated tumors: Results of LITESPARK-015 study. J Clin Oncol. 2025;43(suppl 5):534. doi:10.1200/JCO.2025.43.5_suppl.534