Date: 2017-05-17
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Merus (The Netherlands)
Product: MCLA-128
Action
mechanism: bispecific antibody. MCLA-128 is a full-length IgG bispecific antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity targeting HER2 and HER3 receptors. It is designed to block HER3/heregulin dependent tumor growth and survival as well as enhance immune-mediated killing of 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.
Disease: solid tumors, breast cancer, gastric cancer, ovarian cancer, endometrial cancer, non small cell lung cancer
Therapeutic
area: Cancer - Oncology
Country: France, Italy, The Netherlands, Portugal, Spain
Trial
details: This is a Phase I/II, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, PK, PD, immunogenicity and anti-tumor activity of MCLA-128. (NCT02912949)
Latest
news:
- • On May 17, 2017, Merus 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. 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 metastatic breast cancer 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 metastatic breast cancer 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 metastatic breast cancer patients was 64% (7/11). Evaluation of additional metastatic breast cancer patients and other indications is ongoing.
- With single agent activity established in metastatic breast cancer, Merus also announced plans to initiate a Phase 2, open-label, multicenter, international clinical study to evaluate MCLA-128-based combinations in two metastatic breast cancer populations:
- 1) confirmed HER2-positive metastatic breast cancer patients (progressing on anti-HER2 therapies including TDM-1) who will receive MCLA-128 in combination with trastuzumab and chemotherapy,
- 2) confirmed hormone receptor positive status and HER2-low (IHC HER2 1+ or 2+ and FISH negative for HER2 amplification) metastatic breast cancer 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.
Is
general: Yes
