On December 10, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported clinical data on zenocutuzumab (Zeno) in combination with trastuzumab and vinorelbine in patients (pts) with HER2 positive/amplified (HER2+) metastatic breast cancer (MBC) who had progressed on anti-HER2 antibody drug conjugates (ADC), at the San Antonio Breast Cancer Symposium in San Antonio, Texas (Press release, Merus, DEC 10, 2021, View Source [SID1234596771]).

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Andrew Joe, Chief Medical Officer at Merus, said, "We are pleased to present the final analysis of the triplet Zeno combination which has demonstrated clinically meaningful activity in heavily pretreated patients with HER2+/amplified MBC. We are encouraged by Zeno’s potential to be active in indications outside NRG1 fusion cancers, opening opportunities for potential collaborations in these areas."

The reported data are from the completed phase 2 study, designed to explore the efficacy of a triplet combination of Zeno plus trastuzumab and vinorelbine in MBC patients (NCT03321981). Preliminary results for patients treated with the triplet regimen were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Annual Meeting. The combination was observed to be well-tolerated in the run-in cohort and the cohort was expanded. The primary endpoint of the study was clinical benefit rate (CBR) at 24 weeks of 45%. Updated results from the cohort expansion are presented here:

At the efficacy data cut-off, March 31, 2021, 39 patients, with a median age of 57 and with a median number of five prior therapies, had received the Zeno-based triplet combination, 4 of whom were ongoing. All patients had completed at least 6 months of treatment or discontinued
37 patients with locally confirmed HER2 overexpression (IHC 3+ or IHC 2+/FISH-positive) were evaluable for antitumor activity
The clinical benefit rate (CBR: complete response + partial response + stable disease ≥24 weeks) per investigator assessment was 49% (18/37 patients; 90% CI 34 – 63)
Confirmed responses (per investigator) were reported in 10 patients, including 2 patients with complete response (CR)
Median duration of response was 4.2 months (90% CI 2.8 – 12.4), including 2 patients with CR lasting 4.2 and 7.2+ months, and 8 patients with partial responses (PR) lasting from 2.6 to 12.4 months
Median progression-free survival was 5.5 months (90% CI 4.1 – 5.6); 7 patients (19%) were censored. Estimated overall survival rates at 12 and 24 months were 73% and 61%, respectively
The combination was observed to be well tolerated, with AEs primarily related to chemotherapy
As previously reported, with completion of this phase 2 trial, Merus does not have plans to advance into a phase 3 clinical trial in metastatic breast cancer in the absence of a partner. The company continues to focus on the eNRGy trial to potentially support a BLA submission seeking a tumor agnostic indication for Zeno in patients with previously treated NRG1+ cancers.

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About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.