OncLive’s December Roundup of Key FDA Approvals in Oncology

Below is your guide to all treatment options that the FDA cleared in December 2024. The recap spotlights the topline data that supported the regulatory decisions and features expert insights on what they mean for clinical practice.

12/4: Durvalumab in Limited-Stage Small Cell Lung Cancer

The FDA approved durvalumab (Imfinzi) for use in adult patients with limited-stage small cell lung cancer whose disease has not progressed after concurrent platinum-based chemotherapy and radiation based on findings from the phase 3 ADRIATIC trial (NCT03703297). The immunotherapy significantly improved overall survival (OS) over placebo, translating to a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.57-0.93; P = .0104). The median OS in the respective arms was 55.9 months (95% CI, 37.3-not reached [NR]) and 33.4 months (95% CI, 25.5-39.9).

In a recent interview with OncLive, Suresh Senan, MRCP, FRCR, PhD, full professor of treatment and quality of life, cancer biology and immunology, radiation oncology and professor of clinical experimental radiotherapy at Amsterdam University Medical Centers, discussed the significance of the decision for this population. He said, “[Results from the phase 3 ADRIATIC trial] are very significant…because we’ve actually had very little change in the treatment paradigm for the past 30 years or so.”

OTHER RELATED COVERAGE

• In a recent Peer Exchange program, a panel of experts discussed the interim data from ADRIATIC and underscored the potential clinical relevance of durvalumab in improving life expectancy and its mechanisms of synergy within the tumor microenvironment.
• Earlier this year, Eric Kumar Singhi, MD, assistant professor in the Department of General Oncology in the Department of Thoracic/Head and Neck Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, explained how ADRIATIC sought to address unmet needs in this population.

12/4: Zenocutuzumab in NRG1+ NSCLC and Pancreatic Adenocarcinoma

The regulatory agency awarded accelerated approval to zenocutuzumab-zbco (Bizengri) for use in adult patients with advanced, unresectable, or metastatic non–small cell lung cancer (NSCLC) harboring an NRG1 gene fusion with disease progression on or following systemic therapy; or advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring an NRG1 gene fusion with disease progression on or following systemic therapy.

The agent elicited an overall response rate of 33% (95% CI, 22%-46%) in patients with NSCLC (n = 64) enrolled in the phase 2 eNRGy trial (NCT02912949), with a median duration of response (DOR) of 7.4 months (95% CI, 4.0-16.6). The ORR with the agent in those with pancreatic adenocarcinoma (n = 30) was higher, at 40% (95% CI, 23%-59%) with a median DOR ranging from 3.7 months to 16.6 months.

In a recent interview, Alison Schram, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, discussed the decision, underscoring that zenocutuzumab is the first targeted therapy approved for those with NRG1 fusion–positive cancers:

OTHER RELATED COVERAGE

• In a News Network program on “Advancing Treatment for NRG1 Fusion+ Lung and Pancreatic Cancers,” E. Gabriela Chiorean, MD, of Fred Hutch Cancer Center, discussed the clinical data with zenocutuzumab and its potential in patients with pancreatic cancer. In the same program, Haley M. Hill, PA-C, of the University of Washington, also highlighted preliminary findings with the agent and projected its potential role in both populations.
• This recap of the program spotlights how NRG1 fusion positivity has emerged as a therapeutic target of interest in several tumor types, different testing approaches for these fusions, treatment strategies for those with NRG1 fusion–positive disease, and ongoing research efforts generating excitement.

12/13: Cosibelimab in Metastatic or Locally Advanced Cutaneous Squamous Cell Carcinoma

The regulatory agency gave the green light to cosibelimab-ipdl (Unloxcyt) for use in adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not eligible for curative surgery or radiation based on findings from the phase 1 trial, Study CK-301-101 (NCT03212404). Cosibelimab induced an ORR of 47% (95% CI, 36%-59%) per independent central review assessment in patients with metastatic disease (n = 78) and 48% (95% CI, 30%-67%) in those with locally advanced disease (n = 31). In the respective arms, the median DOR was NR (range, 1.4+ to 34.1+) and 17.7 months (range, 3.7+ to 17.7).

“Today’s FDA approval of Unloxcyt – the first marketing approval for our company – is a significant milestone both for Checkpoint and for patients with advanced CSCC,” James Oliviero, president and chief executive officer of Checkpoint Therapeutics, stated in a news release.

Previously, in December 2023, the biologics license application (BLA) seeking the approval of cosibelimab in this population received a complete response letter (CRL) from the regulatory agency after a multisponsor inspection of the pharmaceutical company’s third-party contract manufacturing organization revealed “approvability issues.” No concerns pertaining to the clinical data package, safety, or labeling of the agent were noted. The BLA was resubmitted to the FDA in July 2024 and accepted later that month.

12/18: Ensartinib in Locally Advanced or Metastatic ALK+ NSCLC

The FDA cleared ensartinib (Ensacove) for the treatment of adult patients with locally advanced or metastatic ALK-positive NSCLC who have not had prior exposure to an ALK inhibitor based on findings from the phase 3 eXALT3 study (NCT02767804). Ensartinib significantly reduced the risk of disease progression or death by 44% vs crizotinib (Xalkori). The median progression-free survival (PFS) in the respective arms was 25.8 months (95% CI, 21.8-not estimable [NE]) and 12.7 months (95% CI, 9.2-16.6; HR, 0.56; 95% CI, 0.40-0.79; P = .0007). No statistically significant difference in OS was observed between the arms (HR, 0.88; 95% CI, 0.63-1.23; P = .4570).

“The approval of ensartinib by FDA brings another new medicine to patients battling ALK-positive NSCLC, expanding the options to optimize treatment in the first-line setting,” Giovanni Selvaggi, chief medical officer of Xcovery Holdings, Inc., stated in a news release. “This result could not have been achieved without the dedication of our team members and the support of patients, physicians, and all stakeholders involved in the clinical development of ensartinib.”

12/20: Encorafenib Plus Cetuximab and Chemo in BRAF V600E+ Metastatic Colorectal Cancer

The regulatory agency awarded accelerated approval to encorafenib (Braftovi) paired with cetuximab (Erbitux) and fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for use in patients with metastatic colorectal cancer (CRC) harboring a BRAF V600E mutation, as detected by an FDA-approved test. In the phase 3 BREAKWATER study (NCT04607421), the encorafenib regimen (n = 110) induced an ORR of 61% (95% CI, 52%-70%) vs 40% (95% CI, 31%-49%) with chemotherapy with or without bevacizumab (Avastin; n = 110; P = .0008). In the respective arms, the median DOR was 13.9 months (95% CI, 8.5-NE) and 11.1 months (95% CI, 6.7-12.7).

“As the first and only combination regimen featuring a BRAF-targeted therapy for this patient population, usable even in first-line treatment, the encorafenib regimen has demonstrated high response rates that are rapid and durable,” Scott Kopetz, MD, PhD, FACP, professor and deputy chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial, stated in a news release. “This represents an encouraging sign of continued disease control and a source of renewed hope for patients.”

In an earlier interview, Kopetz shed light on the investigation of the regimen in BREAKWATER:

OTHER RELATED COVERAGE

• In a prior Peer Exchange program, “Diagnosis and Treatment of Metastatic Colorectal Cancer With a Focus on HER2-Positive Disease,” a panel of experts shared insights on the BREAKWATER trial and how it fits in with other research being done in the landscape.
• In another previous Peer Exchange program, “Evolving Testing and Treatment Strategies in Metastatic Colorectal Cancer,” another panel of experts reviewed early data from BREAKWATER and their significance for those with BRAF V600E–mutated disease.

12/27: Tislelizumab Plus Chemo in PD-L1+ Unresectable or Metastatic Gastric/GEJ Cancer

The regulatory agency cleared tislelizumab-jsgr (Tevimbra) for use in combination with platinum- and fluoropyrimidine-based chemotherapy in the frontline treatment of patients with unresectable or metastatic, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1. The decision is based on findings from the phase 3 RATIONALE-305 study (NCT03777657) in which the tislelizumab regimen significantly improved OS over chemotherapy alone in this population, at a median OS of 15.0 months and 12.9 months, respectively (HR, 0.80; 95% CI, 0.70-0.92; P = .0011).

“Today’s FDA approval of Tevimbra for the treatment of gastric or gastroesophageal junction cancers in PD-L1 positive adult patients marks a significant step forward in our mission to deliver transformative therapies to patients with cancer,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeiGene, stated in a news release. “This is the second US approval for Tevimbra this year, underscoring its potential to address critical needs in oncology. We remain deeply grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible—and we look forward to building on this momentum in 2025.”

In February 2023, the National Medical Products Administration of China approved tislelizumab plus chemotherapy for frontline use in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma with a high PD-L1 expression. Subsequently, in November 2024, the European commission approved first-line tislelizumab plus chemotherapy for use in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) and gastric or GEJ adenocarcinoma.

12/27: Subcutaneous Nivolumab in Advanced or Metastatic Solid Tumors

On the same day, the regulatory agency approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig) for subcutaneous injection across approved adult, solid tumor nivolumab (Opdivo) indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx). Subcutaneous nivolumab has indications in renal cell carcinoma (RCC), melanoma, NSCLC, head and neck squamous cell carcinoma, urothelial carcinoma, CRC, hepatocellular carcinoma, ESCC, gastric cancer, GEJ cancer, and esophageal adenocarcinoma.

The decision is supported by findings from the phase 3 CheckMate 67T trial (NCT04810078), which demonstrated that the lower boundary of 90% confidence interval of geometric mean ratios was not less than 0.8 for both serum nivolumab Cavg over 28 days and Cmin at steady state. In the subcutaneous nivolumab arm (n = 242), the geometric mean of Cavg over 28 days was 77.373 μg/ml (90% CI, 74.555-80.297) vs 36.875 μg/ml (90% CI, 35.565-38.235) in the intravenous (IV) nivolumab arm (n = 245; GMR, 2.098; 90% CI, 2.001-2.200). Moreover, the geometric mean of Cmin at steady state was 122.227 μg/ml (90% CI, 114.552-130.416) in the subcutaneous arm vs 68.901 μg/ml (90% CI, 64.676-73.402) in the IV arm (GMR, 1.774; 90% CI, 1.633-1.927).

In a prior interview, Saby George, MD, FACP, a professor of oncology and medicine, and director of Network Clinical trials in the Department of Medicine at Roswell Park Comprehensive Cancer Center, as well as the associate professor at Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, discussed early safety and efficacy data with subcutaneous nivolumab in patients with clear cell RCC from CheckMate 67T:

In June 2024, the European Medicines Agency validated an extension application for the subcutaneous formulation of nivolumab for use in previously approved solid tumor indications, including as monotherapy, as maintenance monotherapy after nivolumab plus ipilimumab, or in combination with chemotherapy or cabozantinib.

OTHER RELATED COVERAGE

In a Peer Exchange program, “ASCO GU 2024: Updates in the Treatment of Advanced Renal Cell Carcinoma,” Laurence Albigès, MD, PhD, reviewed prior data from CheckMate 67T with subcutaneous vs intravenous nivolumab in patients with previously treated RCC that were presented at the 2024 Genitourinary Cancers Symposium.

Other Noteworthy Decisions:

• On December 17th, the FDA issued a CRL to a BLA seeking the approval of fixed combination amivantamab-vmjq (Rybrevant) and recombinant human hyaluronidase for subcutaneous administration in patients with NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations. The letter was linked with observations made during inspection of the manufacturing facility, not efficacy and safety data submitted with the application.
• On December 18th, the FDA approved remestemcel-L-rknd (Ryoncil) for use in pediatric patients at least 2 months of age with steroid-refractory acute graft-vs-host disease based on findings from the phase 3 MSB-GVHD001 trial (NCT02336230). The agent (n = 54) elicited an ORR of 70% (95% CI, 56.4%-82.0%) at day 28, which comprised a complete response rate of 30% (95% CI, 18.0%-43.6%) and a partial response rate of 41% (95% CI, 27.6%-55.0%).