Two New FDA Approvals in Lung Cancer

The first week of December saw two significant FDA approvals in lung cancer treatment, offering new options for people with hard-to-treat forms of the disease.

Bizengri: “milestone” approval for NRG1-Positive NSCLC

On Dec. 4, 2024, the FDA granted accelerated approval for Bizengri (zenocutuzumab) for the treatment of advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) or pancreatic cancer harboring neuregulin 1 (NRG1) gene fusions, also called NRG1 rearrangements, in adults who have had disease progression with previous treatments.

NSCLC remains the most common type of lung cancer, but NRG1 fusions are considered rare, affecting up to 0.5% of patients with NSCLC. Studies suggests that NRG1 fusion-positive NSCLC responds poorly to standard treatments like chemotherapy and immunotherapy. Bizengri is the first systemic therapy for this genetic subtype, offering new hope for patients and caregivers.

The approval is based on results from the eNRGy study, an open-label trial. Among 64 participants with advanced or metastatic NRG1 fusion-positive NSCLC, the overall response rate (ORR) was 33%, with a median duration of response (DOR) of 7.4 months. For the 30 patients with NRG1 fusion-positive pancreatic cancer, the ORR was 40%, with DORs ranging from 3.7 to 16.6 months.

“The FDA approval of Bizengri marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced, unresectable,\ or metastatic and harbors the NRG1 gene fusion,” Alison Schram, M.D., principal investigator of the ongoing eNRGy trial, stated in a news release. Schram is an oncologist at Memorial Sloan Kettering Cancer Center in New York. “I have seen firsthand how treatment with Bizengri can deliver clinically meaningful outcomes for patients.”

Bizengri is bispecific HER2- and HER3-directed antibody administered as an intravenous infusion every two weeks. Commonly reported side effects include diarrhea, fatigue, nausea, and musculoskeletal pain. Severe laboratory abnormalities were also reported, such as anemia and reduced platelet levels. Bizengri carries a boxed warning for the risk of fetal harm.

Imfinzi approval expanded to treat limited-stage SCLC

On the same day, the FDA also approved a new indication for Imfinzi (durvalumab) for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed after chemotherapy and radiation.

Small cell lung cancer (SCLC) makes up 10% to 15% of lung cancers and grows faster than NSCLC. About one-third of SCLC cases are considered limited-stage at diagnosis, meaning the cancer is confined to one side of the chest. This stage generally responds well to initial radiation and chemotherapy and radiation, though it commonly recurs. Imfinzi’s new indication represents a key advance for patients with LS-SCLC, who historically have had few post-treatment options.

The approval is supported by results from the ADRIATIC clinical trial. In this randomized, double-blind study of 730 patients, monotherapy with Imfinzi significantly improved overall survival (OS) compared to placebo, with a median OS of 55.9 months versus 33.4 months, translating to a 27% reduction in the risk of death. Progression-free survival (PFS) was also significantly longer with Imfinzi, 16.6 months compared to 9.2 months in the placebo group. Commonly reported side effects were lung inflammation (pneumonitis) and fatigue.

Imfinzi is “the first and only systemic treatment following curative-intent, platinum-based chemoradiotherapy to show improved survival for patients with this aggressive form of lung cancer,” Suresh Senan, Ph.D., trial investigator and professor of clinical experimental radiotherapy at the Amsterdam University Medical Center, stated in a news release from AstraZeneca. “This finding represents the first advance for this disease in four decades.”

Imfinzi’s treatment schedule for LS-SCLC aligns with previously approved regimens, typically given as an intravenous infusion every four weeks. Initially approved in 2017, Imfinzi is also indicated for extensive-stage SCLC, certain types of early and advanced NSCLC, as well as various biliary tract, liver, and endometrial cancers.