A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
Solid Tumours Harboring NRG1 Fusion, NSCLC Harboring NRG1 Fusion, Pancreatic Cancer Harboring NRG1 Fusion
About this trial
This is an interventional treatment trial for Solid Tumours Harboring NRG1 Fusion focused on measuring Bispecific Antibody IgG1, HER2, HER3, MCLA-128, Antibodies, Bispecific, Immunologic Factors, NRG1 fusion, NRG1, Solid tumor, Pancreatic cancer, PDAC, Non-small cell lung cancer, NSCLC, zenocutuzumab
Eligibility Criteria
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 - 2;
- 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 for at least 7 days prior to screening;
- Platelets ≥100 x 109/L without transfusion support for at least 7 days prior to screening;
- Hemoglobin ≥8 g/dL or ≥5 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 or no satisfactory alternative treatment options are available;
- Locally-advanced unresectable or metastatic solid tumor malignancy with documented NRG1 gene fusion, identified through molecular assays such as next generation sequencing-based assays [DNA or RNA], 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 without receiving antiviral treatment, 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.
Sites / Locations
- Mayo ClinicRecruiting
- University of California IrvineRecruiting
- Stanford UniversityRecruiting
- Georgetown UniversityRecruiting
- Cancer Specialists of North FloridaRecruiting
- Mayo ClinicRecruiting
- Emory Winship Cancer InstituteRecruiting
- Dana Farber Cancer CenterRecruiting
- Karmanos Cancer CenterRecruiting
- Mayo ClinicRecruiting
- Billings Clinic Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- University of PennsylvaniaRecruiting
- Averra Medical GroupRecruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- Huntsman Cancer InstituteRecruiting
- Utah Cancer SpecialistsRecruiting
- Hematology-Oncology Specialist of FredericksburgRecruiting
- Virginia Mason Hospital & Seattle Medical CenterRecruiting
- Hematology Oncology AssociatesRecruiting
- Northwest Medical SpecialtiesRecruiting
- Salzburger UniversitatsklinikumRecruiting
- UZ LeuvenRecruiting
- Princess MargaretCancer CentreRecruiting
- Centre Leon BerardRecruiting
- Hospital Louis Pradel, FRRecruiting
- Institut Gustave RoussyRecruiting
- Hopital CochinRecruiting
- Hopital CurieRecruiting
- Asklepios Klinik AltonaRecruiting
- Asklepios Kliniken Hamburg GmbHRecruiting
- Deutsches KrebsforschungszentrumRecruiting
- Shaare Zedek Medical CenterRecruiting
- Sheba Medical CenterRecruiting
- Ospedale San RaffaeleRecruiting
- Niguarda Cancer CentreRecruiting
- Istituti Fisioterapici OspitalieriRecruiting
- National Cancer Center HospitalRecruiting
- St. Marianna University School of Medicine HospitalRecruiting
- Osaka International Cancer InstituteRecruiting
- National Cancer Center EastRecruiting
- Samsung Medical CenterRecruiting
- Seoul National University College of MedicineRecruiting
- Severance Hospital- Yonsei Cancer CenterRecruiting
- NKIRecruiting
- Amsterdam Medical CenterRecruiting
- Radboud University Medical CenterRecruiting
- UMC UtrechtRecruiting
- University Hospital OsloRecruiting
- National Cancer Centre of Singapore PTE LTDRecruiting
- Vall D'Hebron Institute of Oncology (VHIO)Recruiting
- START Hospital Fundación Jiménez DiazRecruiting
- START Hospital Universitario Madrid SanchinarroRecruiting
- Hospital 12 de OctubreRecruiting
- Clínica Universidad de NavarraRecruiting
- Instituto Valenciano OncologiaRecruiting
- Karolinska UniversitetssjukhusetRecruiting
- National Taiwan University Hospital 7Recruiting
- Sarah Cannon Research InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion
Part 2 NSCLC cancer harboring NRG1 fusion
Part 2 Solid tumour (basket) harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.