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A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion

Trial Status: Active

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 zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion.

Inclusion Criteria

  • At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 10) in Group H;
  • 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;
  • Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:
  • >14 days or >5 half-lives prior to study entry, whichever is shorter.
  • >14 days for radiotherapy.
  • Recovery from major surgery or other complication to ≤ Grade 2 or baseline ;
  • Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support;
  • Platelets ≥100 x 109/L;
  • Hemoglobin ≥8 g/dL or ≥2.2 mmol/L;
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN; in cases of metastatic liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed; in cases of antecedents of Gilbert's syndrome when total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN will be allowed;
  • Estimated glomerular filtration rate (GFR) of >30 mL/min
  • Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
  • Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy;
  • Locally-advanced unresectable or metastatic solid tumor malignancy with documented NRG1 gene fusion, identified through molecular assays such as PCR, next generation sequencing-based assays [DNA or RNA], or FISH as routinely performed at CLIA or other similarly-certified laboratories.

Exclusion Criteria

  • Pregnant or lactating;
  • Presence of an active uncontrolled infection or an unexplained fever;
  • Known hypersensitivity to any of the components of MCLA-128;
  • Known HIV, active Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
  • Known symptomatic or unstable brain metastases;
  • Patients with leptomeningeal metastases
  • Presence of congestive heart failure or Left Ventricular Ejection Fraction<50% or history of significant cardiac disease, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication.
  • Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
  • Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Arizona

Phoenix
Mayo Clinic Hospital in Arizona
Status: ACTIVE
Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
Contact: Jordi Rodon Ahnert
Phone: 713-563-1930

Study Design : This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed. Part 2 new patient populations examined: - Group F: Patients with NSCLC with documented NRG1 fusion - Group G: Patients with pancreatic cancer with documented NRG1 fusion - Group H: Patients with any other solid tumor with documented NRG1 fusion For these new patient populations, Part 2 will further characterize the safety and tolerability of the selected dose level of zenocutuzumab (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). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described. The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (treatment cycles of 28 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 40 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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Merus N.V.

  • Primary ID MCLA-128-CL01
  • Secondary IDs NCI-2019-06025, 2014-003277-42
  • Clinicaltrials.gov ID NCT02912949