KEY TAKEAWAYS
- The eNRGy phase 2 trial aimed to investigate the efficacy of Zeno in NRG1 fusion-positive NSCLC pts
- The primary endpoint was to determine ORR, and the secondary endpoints were to determine DOR and safety.
- Researchers noticed robust and durable efficacy of Zeno in advanced NRG1+ NSCLC pts.
NRG1 fusions are rare oncogenic drivers in non-small cell lung cancer (NSCLC) and various solid tumors, initiating HER2/HER3 heterodimerization and oncogenic transformation. The bispecific antibody Zenocutuzumab (Zeno) (MCLA-128; Zeno) targets HER3-mediated NRG1 signaling in NRG1+ cancers. Currently under evaluation in the pivotal phase 2 eNRGy study and Early Access Program (EAP), Zeno holds potential as a therapeutic intervention.
Dong-Wan Kim and his team aimed to assess the updated data on Zeno in advanced NRG1+ NSCLC.
Researchers conducted an inclusive analysis involving patients (pts) with advanced NRG1+ NSCLC identified through NGS, irrespective of prior standard therapy candidacy. Inclusion criteria comprised age ≥ 18 years, ECOG PS ≤ 2, and measurable or evaluable disease according to (RECIST v1.1). Zeno (750 mg IV Q2W) was administered until disease progression or unacceptable toxicity. Tumor imaging occurred Q8W, with the primary endpoint being investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints encompassed duration of response (DOR) and safety.
About 85 pts with NRG1+ NSCLC (78 eNRGy/7 EAP) were enrolled by February 01, 2023. The efficacy analysis included 65 pts who received ≥ 1 dose of Zeno and were enrolled by August 01, 2022, ensuring ≥ 6 months of follow-up and meeting primary efficacy criteria. Median age was 64 years (range 32–86), 65% female, and 29%/63%/5% with ECOG PS 0/1/2 (missing 2 pts). Predominantly Asian (52%) or White (37%), 77% had visceral metastases, 98% adenocarcinoma histology, and 1 pt had non-measurable disease. CD74 (52%) and SLC3A2 (23%) were common fusion partners.
Patients received a median of 2 prior systemic therapies (range 0-6), 78% with platinum-based chemotherapy; 12% were treatment-naïve. In 64 pts with measurable disease, confirmed ORR was 34% (22/64; 95% CI 23-47). 78% (50/64) had target lesion reduction. Median DOR was 12.9 months with ongoing responses in 11/22 (50%) pts. Kaplan-Meier estimate of the 6-month DOR rate was 79%. Among 85 pts treated, Grade ≥ 3 individual adverse events(AEs) occurred in < 4% of pts. No patient discontinued Zeno for a treatment-related AE.
The study concluded that Zeno demonstrates robust and enduring efficacy in advanced NRG1+ NSCLC, accompanied by a well-tolerated safety profile, underscoring its potential as a promising therapeutic option for this patient population.
The study is sponsored by Merus N.V.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT02912949
Kim D W, Goto K, Schram A, et al. (2023). “Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC).” Presented at ESMO ASIA 2023 (Abstract 595P).
