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A Study of MCLA-128 in Patients With Solid Tumors

Descriptive Information
Brief Title † A Study of MCLA-128 in Patients With Solid Tumors
Official Title † A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors
Brief Summary 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
Detailed Description Study Design : This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed. Part 2 patient populations of interest to receive the RP2D determined in Part 1 are: - relapsed/refractory HER2-amplified breast cancer (Group A); - advanced/metastatic epithelial ovarian cancer (Group C); - advanced/metastatic HER2-amplified gastric cancer or esophageal-gastric junction adenocarcinoma (Group D); . - advanced/metastatic endometrial cancer (Group E); - advanced/metastatic or recurring HER2 expressing non small cell lung cancer (Group F); Part 2 will further characterize the safety and tolerability of the selected dose level of MCLA-128, as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 12 weeks in duration). The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (first dose of study drug until the last dose of study drug with treatment cycles of 21 days); and Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 2 years). Participants' safety will be monitored throughout the study. Number of Sites: Up to 10 sites are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Number of participants with Dose Limiting Toxicities (DLT)
Secondary Outcome Measure † Incidence of Treatment Related AE [safety and tolerability]
Condition † Malignant Solid Tumour Breast Cancer Gastric Cancer Ovarian Cancer Endometrial Cancer Non Small Cell Lung Cancer
Intervention † DrugMCLA-128
Study Arms / Comparison Groups Part 1 Dose Escalation Cohorts receiving escalating doses of MCLA-128 until MTD or RP2D is reached. Each Cycle is 21 days. Single agent treatment. Part 2 breast cancer Participants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days. Part 2 ovarian cancer Participants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days. Part 2 gastric/GE junction cancer Participants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days. Part 2 endometrial cancer Participants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days. Part 2 non small cell lung cancer Participants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 130
Start Date † January 2015
Completion Date December 2018
Primary Completion Date December 2018
Eligibility Criteria † Inclusion Criteria: - At least one measurable lesion according to RECIST v1.1; - Performance status of ECOG 0 or 1; - Estimated life expectancy of at least 12 weeks; - Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1; - At least a 4-week interval since last received radiotherapy; - Recovery from major surgery; - Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support; - Platelets ≥100 x 109/L; - Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent); - Total bilirubin 5 x ULN; - Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of >50 mL/min - coagulation function (INR, and aPTT ≤1.5 x ULN , unless on therapeutic anticoagulants); - Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine - Able to provide a tumor biopsy sample (preferably fresh or else archival); if archival: taken within 2 years from screening; - Not pregnant or nursing - Fertile patients must use effective contraception during and for 6 month after completion of study therapy; - Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit Specific Inclusion Criteria for Part 2 (Group A) breast cancer (BC): - Histologically-confirmed and documented advanced / metastatic BC, relapsed/refractory to at least 2 prior HER2 directed regimen for BC; - Confirmed HER2 amplification based on historical pathology report or analysis of baseline fresh/archival tumor sample. Specific Inclusion Criteria for Part 2 (Group C) ovarian cancer (OC): - Histologically-confirmed and documented advanced/metastatic epithelial OC for which no curative therapy is available; - Prior therapy including all available standard therapies and at least 1 platinum based chemotherapy. Specific Inclusion Criteria for Part 2 (Group D) gastric or esophageal-gastric junction cancer (GC or GEC): - Histologically-confirmed and documented advanced/metastatic GC or GEC ; - Prior chemotherapy including platinum and fluoropyrimidine based treatment and trastuzumab - Confirmed HER2 amplification based on historical pathology report or analysis of fresh/archival tumor sample. Specific Inclusion Criteria for Part 2 (Group E) endometrial cancer (EC): - Histologically-confirmed and documented advanced/metastatic EC for which no curative therapy is available; - Prior therapy including all available standard therapies and at least 1 prior chemotherapy. Specific Inclusion Criteria for Part 2 (Group F) Non small cell lung cancer (NSCLC): - Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC; with pathological characterization of non-squamous or squamous histological subtype and adenocarcinoma subtype classification; - Confirmed HER2 expression (by IHC) based on historical pathology report or analysis of baseline (fresh or archival) tumor sample; - Prior treatment included all available standard therapies with at least one regimen of platinum-based chemotherapy in locally advanced/metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment; - Patients with ALK fusion oncogene with documented disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC; - Patients with known mutation in the EGFR gene must have documented disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC. Exclusion Criteria: - Pregnant or lactating; - Presence of an active infection or an unexplained fever; - Known hypersensitivity to any of the components of MCLA-128; - Known HIV, Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible - Any untreated central nervous system lesion - Patients with leptomeningeal metastases - Presence of congestive heart failure or Left Ventricular Ejection Fraction
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Ernesto Wasserman, MD, +31302538800, enquiries@merus.nl
Location Countries † France
Administrative Information
NCT ID † NCT02912949
Organization ID MCLA-128-CL01
Secondary IDs †† 2014-003277-42
Responsible Party Sponsor
Study Sponsor † Merus N.V.
Collaborators †† Chiltern International Inc.
Investigators † Principal Investigator: Anthony Tolcher, MD, Independent protocol advisor
Information Provided By
Verification Date March 2017
First Received Date † August 16, 2016
Last Updated Date March 24, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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