Efficacy and safety of zenocutuzumab in advanced pancreas cancer and other solid tumors harboring NRG1 fusions.

• DOI: 10.1200/jco.2021.39.15_suppl.3003
• Publication Date: 2021-06-02T14:00:38Z
• Authors: Alison M. Schram; Eileen Mary O'Reilly; Grainne M. O'Kane; Koichi Goto; Dong-Wan Kim; Cindy Neuzillet; Patricia Martin-R...; Michaël Duruisseaux; Misako Nagasaka; Jordi Rodon; Benjamin Adam Wei...; Kumiko Umemoto; Sai-Hong Ignatius Ou; Teresa Macarulla; Christelle De La ...; Andrew K. Joe; Ernesto Wasserman; Viktoriya Stalbov...; Jim Ford; Alexander E. Drilon
• Keywords: Clinical endpoint

3003 Background: NRG1 fusion proteins are oncogenic drivers in pancreas cancer and other solid tumors. They bind HER3, leading to HER2/HER3 heterodimerization transformation. The activity of zenocutuzumab (MCLA-128; zeno), a bispecific antibody targeting signaling positive ( NRG1+) cancers, is being evaluated the ongoing global multicenter phase 2 part eNRGy study early access program (EAP). Methods: Enrolled patients (pts) have advanced NRG1+ cancer, non-small cell lung (NSCLC), tumors previously treated with standard therapy, ≥ 18 years-old, ECOG ≤1, adequate organ function, measurable disease (RECIST v1.1). Zeno dosing: 750 mg IV every weeks until progression or unacceptable toxicity. Primary endpoint: investigator (INV)-assessed objective response rate (ORR). Secondary endpoints: ORR per central independent radiologist review, duration (DOR), safety. Tumor imaging conducted 8 weeks. Results: 51 pts received zeno, 37 14 EAP. As 12 Jan 2021, treatment 27/51 (8/13 pancreas, 10/25 NSCLC, 9/13 tumors). Among pts, 10 5 had opportunity for ≥1 tumor assessment (TA) included this analysis. median age was 49 y (range 34-72), 50% were male, 6/4 0/1, all metastatic KRAS wild-type. number prior therapies 3 1-6). INV-assessed confirmed 40% (4/10; 90% CI, 15;70), cohort responses occurred at first TA. regression seen 7/10 control (90% 61-100). A CA 19-9 decline observed 9/9 (100%) pts. DOR pending. In overall population, 25 33 9 (ORR 27%; 15;43), including who afatinib. well tolerated no requiring dose reduction Across cohorts, individual AEs, grade events reported ≤5% there notable lack cardiotoxicity severe gastrointestinal skin Updated data from cohorts (pancreas, tumors) will be presented. Conclusions: induces rapid major radiologic biomarker heavily-pretreated wild-type minimal promising novel targeted therapeutic option cancers. Clinical trial information: NCT02912949.