Dr Schram on the FDA Approval of Zenocutuzumab in NRG1+ NSCLC and Pancreatic Cancer

Alison Schram, MD, medical oncologist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the FDA approval of zenocutuzumab-zbco (Bizengri, formerly MCLA-128) for the treatment of adult patients with advanced, unresectable, or metastatic non–small cell lung cancer (NSCLC) or pancreatic cancer harboring an NRG1 fusion with disease progression on or after prior systemic therapy.

The approval was supported by data from the phase 1/2 eNRGy trial (NCT02912949).

Schram notes the significance of this regulatory decisions as the first targeted therapy approved for patients with NRG1 fusion–positive cancers, explaining that this agent represents a much-needed treatment option for this group. Patients with NRG1 fusion–positive NSCLC have a poor prognosis and generally have worse outcomes with standard-of-care to chemotherapy and immunotherapy, she says. Schram adds that patients with pancreatic cancer have limited treatment options following first- and second-line chemotherapy.

Findings from eNRGy demonstrated that in a cohort of patients with pancreatic ductal adenocarcinoma (n = 33), zenocutuzumab elicited an investigator-assessed overall response rate (ORR) of 42.4% (95% CI, 25.5%-60.8%) per RECIST 1.1 criteria. Patients with NSCLC (n = 79) achieved an investigator-assessed ORR of 37.2% (95% CI, 26.5%-48.9%) per RECIST 1.1 criteria.

In the PDAC cohort, patients experienced a median time to response (TTR) of 1.8 months (range, 1.6-5.4) and a median duration of response (DOR) of 9.1 months (95% CI, 5.5-12.0) per investigator assessment and RECIST 1.1 criteria. The estimated 6-month DOR rate was 71% (95% CI, 41%-88%).

Patients with NSCLC achieved a clinical benefit rate of 61.5% (95% CI, 49.8%-72.3%). The median TTR was 1.8 months (range, 1.5-13.0), and the median DOR was 14.9 months (95% CI, 7.4-20.4). The estimated 6- and 12-month DOR rates were 81% (95% CI, 60%-92%) and 57% (95% CI, 34%-75%), respectively.

Regarding safety in patients with NRG1 fusion–positive solid tumors who received the zenocutuzumab at 750 mg once every 2 weeks (n = 179), treatment-emergent adverse effects (TEAE) occurred in 61% of patients, including 6% of patients who had grade 3/4 TEAEs.

The most common TEAEs reported in at least 10% of patients included diarrhea (any-grade, 17%; grade 3/4, 2%), infusion-related reactions (12%; 0%), fatigue (10%; 0%), nausea (8%; 1%), vomiting (6%; 1%), anemia (4%; 1%), constipation (3%; 0%), increased alanine aminotransferase levels (3%; 1%), increased aspartate aminotransferase levels (3%; 1%), decreased appetite (3%; 1%), and abdominal pain (2%; 1%).