Merus N.V, a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutics, has announced the results of their first-in-human phase 1/2 study of MCLA-128 in solid tumors, including final phase 1 data and promising preliminary activity in patients with HER2-positive Metastatic Breast Cancer (MBC) from the phase 2 portion of the trial. MCLA-128 is a full-length IgG bispecific antibody with enhanced Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) activity targeting HER2 and HER3 receptors. The results will be presented in a poster session on the morning of June 5, 2017 at the American Society of Clinical Oncology (ASCO) Annual Meeting.

In the Phase 1 portion of the Phase 1/2 study, the recommended Phase 2 dose (RP2D) for future studies with MCLA-128 was established as 750 mg every 3 weeks, based on safety and pharmacokinetic data. The Phase 2 portion of the study is ongoing, exploring selected metastatic indications including breast, endometrial, ovarian, gastric and non-small cell lung cancers.  MCLA-128 was well tolerated, with the ongoing Phase 2 portion confirming the safety profile seen in the dose escalation cohort. The most frequent adverse events observed were mild (G1/G2) infusion-related reactions and gastrointestinal toxicities.  No clinically significant cardiotoxicity was reported.

As part of the ongoing study, a cohort of 11 HER2-positive MBC patients has been treated with single agent MCLA-128 (9 patients at RP2D and 2 patients at 480 mg q3 weeks from part 1). These MBC patients were all heavily pretreated, having received a median of 6 prior lines of metastatic therapy, all having 2-5 prior HER2 inhibitor therapies, and some of the patients with outright disease progression to the last line of therapy.  One MBC patient achieved a confirmed partial response (>8+ months) and 7 had stable disease (including 4 sustained stabilizations lasting =5 months).  The clinical benefit rate (complete and partial responses plus stable disease lasting at least 12 weeks) among the cohort of MBC patients was 64% (7/11).  Evaluation of additional MBC patients and other indications is ongoing.

With single agent activity established in MBC, Merus also announced today plans to initiate a Phase 2, open-label, multicenter, international clinical study to evaluate MCLA-128-based combinations in two MBC populations: 1) confirmed HER2-positive MBC patients (progressing on anti-HER2 therapies including TDM-1) who will receive MCLA-128 in combination with trastuzumab and chemotherapy, and 2) confirmed hormone receptor positive status and HER2-low (IHC HER2 1+ or 2+ and FISH negative for HER2 amplification) MBC patients progressing on hormone therapies and CDK4/6 who will receive MCLA-128 in combination with fulvestrant.  In addition to these early clinical results, study of MCLA-128 in these combinations and populations is supported by activity observed in preclinical models.  This Phase 2 study is expected to be launched in Europe and the US in the second half of 2017.

“These clinical results demonstrate that single agent MCLA-128 is active and well tolerated in heavily pretreated metastatic breast cancer patients,” said Professor Josep Tabernero, MD, PhD, Head of Medical Oncology and the Institute of Oncology at Vall d'Hebron University Hospital.  “This positions MCLA-128 as a promising agent for further development as combination therapy in the treatment paradigm of metastatic breast cancer.  I look forward to seeing how these results translate in the planned Phase 2 combination studies.”

“With demonstrated activity in an aggressive disease population, our goal now is to understand where MCLA-128, in combination with current standards of care, can address unmet needs in this disease and deliver improved outcomes and greater optionality to patients in need,” said Ton Logtenberg, Ph.D., chief executive officer of Merus.  “We see opportunities in HER2-positive MBC and hormone-resistant estrogen receptor positive MBC, where escape from hormone therapy is often via HER2/3 signaling.  We also look forward to continuing to evaluate MCLA-128 in other tumor types, including endometrial, ovarian, gastric and NSCLC cancers in this ongoing study.”