The FDA has extended the Prescription Drug User Fee Act (PDUFA) target action date for zenocutuzumab, a biologics license application (BLA) seeking approval for patients with NRG1-positive (NRG1+) non-small cell lung cancer (NSCLC) and pancreatic cancer. The new target date is set for February 4, 2025.
The FDA's decision to extend the review period comes after granting priority review to the BLA in May 2024. According to Merus NV, the developer of zenocutuzumab, the extension is needed to allow the FDA additional time to assess information provided in response to a request related to chemistry, manufacturing, and controls. The FDA did not request any additional clinical data.
The BLA is supported by data from the phase 1/2 eNRGy trial (NCT02912949), a global, multicenter study that enrolled patients aged 18 or older with locally advanced, unresectable, or metastatic solid tumors harboring NRG1 fusions, including NSCLC and pancreatic ductal adenocarcinoma (PDAC). These patients had been previously treated with or were ineligible for standard-of-care therapy and had an ECOG performance status of 0 to 2.
Promising Results from eNRGy Trial
In the eNRGy trial, patients received 750 mg of intravenous zenocutuzumab every two weeks until disease progression. Tumor assessments were conducted every eight weeks. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST 1.1 criteria, with secondary endpoints including duration of response (DOR), central-assessed ORR, and safety.
Among patients with NSCLC harboring NRG1 fusions (n = 79), the investigator-assessed ORR was 37.2% (95% CI, 26.5%-48.9%) per RECIST 1.1 criteria, and the clinical benefit rate (CBR) was 61.5% (95% CI, 49.8%-72.3%). The median time to response was 1.8 months (range, 1.5-13.0), and the median DOR was 14.9 months (95% CI, 7.4-20.4). The DOR rates at 6 and 12 months were 81% (95% CI, 60%-92%) and 57% (95% CI, 34%-75%), respectively.
In the PDAC arm of the trial (n = 33), zenocutuzumab led to an investigator-assessed ORR of 42.4% (95% CI, 25.5%-60.8%) per RECIST 1.1 criteria. One patient achieved a complete response, and the remaining responders had partial responses. The stable disease rate was 45%, and the CBR was 72.7% (95% CI, 54%-87%). The median DOR was 9.1 months (95% CI, 5.5-12.0), and the 6-month DOR rate was 71% (95% CI, 41%-88%).
Manageable Safety Profile
Safety data from 189 patients with NRG1+ solid tumors treated with zenocutuzumab at 750 mg every two weeks showed that treatment-emergent adverse events (TEAEs) were manageable, with no patients discontinuing therapy due to TEAEs. No grade 5 treatment-related TEAEs were reported.
Any-grade TEAEs of any cause occurred in 88% of patients, while grade 3 or 4 TEAEs were reported in 35%. Common TEAEs included diarrhea (28% any-grade; 2% grade 3/4), infusion-related reactions (28%; 2%), and fatigue (12%; 0%).
