A Snapshot of April FDA Approvals in Oncology for Nurses and APPs

Multiple indications were approved for nivolumab plus ipilimumab and for penpulimab-kcqw.

During the month of April, several treatments in oncology were approved by the FDA. The approvals encompassed a number of cancer types, including breast, colorectal r (CRC), ovarian, and hepatocellular carcinoma (HCC), among others.

Some approved therapeutic regimens included 2 new indications for the combination use of nivolumab (Opdivo) plus ipilimumab (Yervoy), and for penpulimab-kcqw. In addition, bevacizumab-nwgd (Jobevne), a biosimilar for bevacizumab (Avastin), was approved across multiple solid tumor types.¹

The full list of new therapies in cancer approved by the FDA in April is below.

1. Nivolumab Plus Ipilimumab for Unresectable/Metastatic MSI-H/dMMR CRC

On April 8, the FDA approved the use of nivolumab plus ipilimumab in adult and pediatric patients aged 12 or older with unresectable/metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) CRC, per an announcement from the agency.²

The efficacy and safety of nivolumab/ipilimumab and single-agent nivolumab for the approved indication was investigated in the randomized, 3-arm, open-label CHECKMATE-8HW trial (NCT04008030), evaluating nivolumab monotherapy, the combination therapy, or chemotherapy.

In the first-line setting, median progression-free survival (PFS) was not reached (NR; 95% CI, 38.4-not estimable [NE]) for patients in the nivolumab/ipilimumab arm and 5.8 months (95% CI, 4.4-7.8) for those in the chemotherapy arm (hazard ratio [HR], 0.21; 95% CI, 0.14-0.32; P < .0001). Data on objective response rates (ORR) and overall survival (OS) were not available at the time of interim PFS analysis.

The most commonly reported adverse events (AEs), which were reported in at least 20% of those treated with nivolumab/ipilimumab, were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. Likewise, the most common AEs for those on nivolumab monotherapy, were fatigue, diarrhea, abdominal pain, pruritic, and musculoskeletal pain.

With this announcement, the FDA also stated that the accelerated approval of nivolumab monotherapy for adult and pediatric patients of at least 12 years of age with MSI-H or dMMR metastatic CRC who have progressed after fluoropyrimidine, oxaliplatin, and irinotecan, has been converted to regular approval.

2. Larotrectinib in NTRK Fusion-Positive Solid Tumors

The FDA approved larotrectinib (Vitrakvi) for use in adult and pediatric patients who have neurotrophic receptor tyrosine kinase (NTRK) gene fusion-positive solid tumors and no known acquired resistance mutation, where tumors are metastatic or where resection will likely cause severe morbidity, and have no appropriate alternative treatments or have progressed after treatment, per an announcement from Bayer on April 10.³

The first-in-class oral tropomyosin receptor kinase (TRK) inhibitor displayed clinically meaningful and durable response in several NTRK fusion-positive solid tumors. The approval is based on results from multicenter, open-label, single-arm clinical trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

Efficacy results pooled from the trials found an ORR of 60% (95% CI, 55%-65%). Rate of complete response (CR) and partial response (PR) were 24% and 36%, respectively. Of those who demonstrated CRs, 5% showed pathological CR.

Participants who underwent surgical resection with negative margins and no viable tumor cells found in post-operative pathologic assessment experienced CR as long as no other disease sites were detectable. Median duration of response (DOR) for patients taking larotrectinib was 43.3 months (95% CI, 32.5-NE).

Serious AEs included central nervous system issues, bone fractures, and liver issues.

Including lab abnormalities, the most frequent AEs, occurring in at least 20% of patients taking larotrectinib were increased AST (62%), increased ALT (61%), anemia (45%), hypoalbuminemia (44%), musculoskeletal pain (41%), increased alkaline phosphatase (40%), leukopenia (37%), lymphopenia (35%), neutropenia (34%), hypocalcemia (32%), fatigue (31%), vomiting (30%), cough (29%), constipation (27%), pyrexia (26%), diarrhea (26%), nausea (25%), abdominal pain (24%), dizziness (22%), and rash (21%).

3. Nivolumab Plus Ipilimumab in Metastatic/Unresectable HCC

The FDA announced its approval of frontline nivolumab plus ipilimumab for use in adult patients with unresectable or metastatic HCC on April 11, according to an announcement from the agency.⁴

The approval is based on data from the open-label CHECKMATE-9DW trial (NCT04039607), which randomized 668 participants 1:1 to receive either 1 mg/kg of nivolumab intravenously plus 3 mg/kg of ipilimumab intravenously every 3 weeks for a maximum of 4 doses, followed by 480 mg of intravenous nivolumab monotherapy every 4 weeks, or investigator’s’ choice of lenvatinib (Lenvima) or sorafenib (Nexavar).

Median OS was 23.7 months (95% CI, 18.8-29.4) in the nivolumab/ipilimumab arm and 20.6 months (95% CI, 17.5-22.5) in the lenvatinib or sorafenib arm (HR, 0.79; 95% CI, 0.65-0.96; P < .0180).

ORRs in the experimental arm and control arm were 36.1% (95% CI, 31.0%-41.5%) and 13.2% (95% CI, 9.8%-17.3%; P < .0001), respectively.

The AEs most frequently reported, occurring in over 20% of patients, were rash, pruritic, fatigue, and diarrhea.

4. Penpulimab-kcqw in Non-Keratinizing Nasopharyngeal Carcinoma

On April 23, the FDA approved penpulimab-kcqx with cisplatin or carboplatin and gemcitabine for the frontline treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC), in addition to approving penpulimab-kcqx monotherapy for adults with metastatic non-keratinizing NPC whose disease has progressed on or after platinum-based chemotherapy and 1 or more previous lines of therapy.⁵

The efficacy of the former approval was assessed in the randomized, double-blind, multicenter trial Study AK105-304 (NCT04974398), in which 291 patients with recurrent/metastatic NPC who had not received prior systemic chemotherapy were treated with either penpulimab-kcqx plus cisplatin or carboplatin and gemcitabine preceding penpulimab-kcqx, or placebo plus cisplatin or carboplatin and gemcitabine preceding placebo.

Median PFS in the penpulumab-kcqx arm was 9.6 months (95% CI, 7.1-12.5), compared with 7.0 months (95% CI, 6.9-7.3) in the placebo arm (HR, 0.45; 95% CI, 0.33-0.62; 2-sided P < .0001). After 12 months of follow-up, 31% and 11% of patients in each respective arm were alive and progression free.

The efficacy of penpulimab-kcqx was determined in the open-label, multicenter, single-arm Study AK105-202 (NCT03866967) trial. The trial assessed 125 patients with unresectable or metastatic non-keratinizing NPC whose disease progressed after platinum-based chemotherapy and 1 or more other lines of therapy. Median DOR was not reached (95% CI, 9.2-NE), and ORR was 28% (95% CI, 20%-37%).

Several immune-mediated AEs were observed with penpulimab-kcqx, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

5. Ready-to-Dilute Thiotepa for Breast and Ovarian Adenocarcinomas

The FDA has approved a ready-to-dilute, multi-dose formulation of thiotepa (Tepylute) for use in breast and ovarian adenocarcinomas, according to a news release on April 29 from Shorla Oncology, the US-Ireland pharmaceutical company that developed the product.⁶

This approval covers 15 mg and 100 mg/10mL vials of thiotepa for treatment and is the first approved multi-dose formulation of thiotepa. According to the release, the vial will be stable for 14 days when properly stored.

The vial may reduce preparation time and will not require reconstitution, unlike the standard-of-care freeze-dried powder formulation, which has been produced as such since the 1950s. According to Shorla Oncology’s website, this formulation may reduce manual compounding time by 30% compared with lyophilized thiotepa.⁷

Additional adverse events associated with ready-to-dilute thiotepa include infection, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, and central nervous system toxicity.⁸ The formulation can cause fetal harm if administered to a patient who is pregnant.

Those with severe hypersensitivity to thiotepa are not advised to receive this formulation of thiotepa, nor are those with live or attenuated vaccines. The drug may cause severe myelosuppression and may be carcinogenic in humans.^7,8

References

1. Biocon Biologics Announces U.S. FDA Approval for Jobevne™, Biosimilar Bevacizumab, Expanding Its Oncology Portfolio. News Release. Biocon Biologic, Ltd. April 10, 2025. Accessed April 10, 2025. https://www.bioconbiologics.com/biocon-biologics-announces-u-s-fda-approval-for-jobevne-biosimilar-bevacizumab-expanding-its-oncology-portfolio/
2. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. FDA. April 8, 2025. Accessed April 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-msi-h-or-dmmr-colorectal-cancer
3. U.S. FDA Grants Full Approval of VITRAKVI^® (larotrectinib) for Adult and Pediatric Patients with NTRK Gene Fusion-Positive Solid Tumors. News Release. Bayer. April 10, 2025. Accessed April 10, 2025. businesswire.com/news/home/20250409395229/en/U.S.-FDA-Grants-Full-Approval-of-VITRAKVI-larotrectinib-for-Adult-and-Pediatric-Patients-with-NTRK-Gene-Fusion-Positive-Solid-Tumors
4. FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma. FDA. April 11, 2025. Accessed April 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma
5. FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. FDA. April 23, 2025. Accessed April 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma
6. Shorla Oncology Announces FDA Approval of TEPYLUTE® 100mg, First and Only Ready-to-Dilute Multi-Dose Vial of Thiotepa to Treat Breast and Ovarian Cancer and Commercial Launch of TEPYLUTE 15mg and 100mg Vials in the U.S. Shorla Oncology. April 29, 2025. Accessed April 29, 2025. https://www.businesswire.com/news/home/20250429747360/en/Shorla-Oncology-Announces-FDA-Approval-of-TEPYLUTE-100mg-First-and-Only-Ready-to-Dilute-Multi-Dose-Vial-of-Thiotepa-to-Treat-Breast-and-Ovarian-Cancer-and-Commercial-Launch-of-TEPYLUTE-15mg-and-100mg-Vials-in-the-U.S.
7. Tepylute (thiotepa) injection. Shorla Oncology. Accessed April 29, 2025. https://shorlaoncology.com/product/tepylute/
8. Tepylute package insert. Updated February, 2025. Accessed April 29, 2025. https://shorlaoncology.com/tepylute-pi/