Merus Announces Promising Results from MCLA-128 Phase 1/2 Study in Metastatic Breast Cancer
Results to be presented at the 2017
Phase 2 clinical trial to be initiated in second half of 2017 exploring two metastatic breast cancer populations: HER2-positive patients and hormone receptor-positive/HER2-low patients
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
“These clinical results demonstrate that single agent MCLA-128 is active and well tolerated in heavily pretreated metastatic breast cancer patients,” said Professor
“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.”
MCLA-128 is designed to block HER3/heregulin-dependent tumor growth and survival as well as enhance immune-mediated cytotoxicity in tumors. MCLA-128 employs a ‘dock and block’ mechanism in which the mode of HER2 receptor binding orientates the HER3 binding arm to effectively block oncogenic signaling through the HER2:HER3 heterodimer even under high heregulin concentrations. In addition, MCLA-128 is engineered for enhanced ADCC in order to recruit and activate immune effector cells to directly kill tumor cells.
Merus is a clinical-stage immuno-oncology company developing innovative full-length human bispecific antibody therapeutics, referred to as Biclonics®. Biclonics® are based on the full-length IgG format, are manufactured using industry standard processes and have been observed in preclinical studies to share several features of conventional monoclonal antibodies, such as long half-life and low immunogenicity. Merus' lead bispecific antibody candidate, MCLA-128, is being evaluated in a Phase 1/2 clinical trial in
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