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

Phase 2

Active, not recruiting

• Conditions: NSCLC Harboring NRG1 Fusion; Pancreatic Cancer Harboring NRG1 Fusion; NRG1 Fusion; Solid Tumours Harboring NRG1 Fusion
• Interventions: Drug: zenocutuzumab (MCLA-128)

• Registration Number: NCT02912949
• Lead Sponsor: Partner Therapeutics, Inc.

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

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 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 examine:

* Group F: Patients with NSCLC with documented NRG1 fusion

* Group G: Patients with pancreatic adenocarcinoma 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 24 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.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2016-08-16
• Study First Submitted QC: 2016-09-22
• Study First Posted: 2016-09-23
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 15) 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:

  1. more than 14 days or more than 5 half-lives prior to study entry, whichever is shorter.
  2. more than 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 ≥75 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 more than 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 LVEF below 50% on the screening echocardiogram; or history or presence of any significant cardiovascular disease, including unstable angina or myocardial infarction within 12 months prior to screening, congestive heart failure (NYHA Class III or IV), 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 ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion	zenocutuzumab (MCLA-128)	Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Part 2 NSCLC cancer harboring NRG1 fusion	zenocutuzumab (MCLA-128)	Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Part 2 Solid tumour (basket) harboring NRG1 fusion	zenocutuzumab (MCLA-128)	Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.

Primary Outcome Measures

Name	Time	Method
Objective overall response rate (ORR) as per local investigator's assessment	36 months	Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Duration of response per RECIST v1.1 as per local Investigator's assessment.	36 Months	To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally

Secondary Outcome Measures

Name	Time	Method
Overall response rate as per Blinded Independent Central Review (BICR)	36 months	Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1 as assessed centrally
Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and BICR	36 months	CBR assessed as the proportion of patients in whom a complete response (CR) or partial response (PR) or stable disease (SD) is observed (where SD duration is a minimum of 24 weeks) by RECIST v1.1 .
Duration of Response as per BICR	36 months	To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed centrally
Time to response per RECIST v1.1. as per local investigator assessment	36 months	To assess time to onset of response in patients with NRG1 fusions as assessed locally
Time to response per RECIST v1.1. as per BICR	36 months	To assess time to onset of response in patients with NRG1 fusions as assessed centrally
Characterize the safety and tolerability of zenocutuzumab (MCLA-128)	6-12 months	Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)
Maximum plasma concentration [Cmax]	36 months	Assess the Cmax of zenocutuzumab (MCLA-128)
Volume of distribution [V]	36 months	Assess the volume of distribution of zenocutuzumab (MCLA-128)
Volume of distribution at steady state [Vss]	36 months	Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state
Area under the concentration versus time curve from time zero to time t [AUC0-t]	36 months	Assess the Area under the concentration versus time curve from time zero to time t \[AUC0-t\] of zenocutuzumab (MCLA-128)
half-life [t1/2]	36 months	Assess the half-life of zenocutuzumab (MCLA-128)
area under the concentration versus time curve [AUC0-∞]	36 months	Assess the area under the concentration versus time curve \[AUC0-∞\] of zenocutuzumab (MCLA-128)
time to reach maximum concentration [tmax]	36 months	Assess the time to reach maximum concentration \[tmax\] of zenocutuzumab (MCLA-128)
Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)	36 months	Assess the Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
serum titers of anti-drug antibodies	36 months	Assess serum titers of anti-drug antibodies
Evaluation of progression free survival (PFS)	36 months
Evaluation of overall survival (OS)	12 months

Trial Locations

Locations (62)

Georgetown University; 🇺🇸 District of columbia, District of Columbia, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

The Oncology Institute of Hope and Innovation; 🇺🇸 Cerritos, California, United States

Sharp Memorial Hospital; 🇺🇸 San Diego, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of California Irvine; 🇺🇸 Irvine, California, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Memorial Cancer Institute; 🇺🇸 Hollywood, Florida, United States

Cancer Specialists of North Florida; 🇺🇸 Jacksonville, Florida, United States

Northwest Oncology & Hematology; 🇺🇸 Rolling Meadows, Illinois, United States

Dana Farber Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Center; 🇺🇸 Detroit, Michigan, United States

Billings Clinic Cancer Center; 🇺🇸 Billings, Montana, United States

St. James Healthcare; 🇺🇸 Butte, Montana, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Averra Medical Group; 🇺🇸 Sioux Falls, South Dakota, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Utah Cancer Specialists; 🇺🇸 Salt Lake City, Utah, United States

Hematology-Oncology Specialist of Fredericksburg; 🇺🇸 Fredericksburg, Virginia, United States

Virginia Mason Hospital & Seattle Medical Center; 🇺🇸 Seattle, Washington, United States

Hematology Oncology Associates; 🇺🇸 Spokane, Washington, United States

Northwest Medical Specialties; 🇺🇸 Tacoma, Washington, United States

Salzburger Universitatsklinikum; 🇦🇹 Salzburg, Austria

UZ Leuven; 🇧🇪 Leuven, Belgium

Princess MargaretCancer Centre; 🇨🇦 Toronto, Ontario, Canada

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Centre Leon Berard; 🇫🇷 Lyon, France

Hospital Louis Pradel, FR; 🇫🇷 Lyon, France

Institut Gustave Roussy; 🇫🇷 Paris, France

Hopital Cochin; 🇫🇷 Paris, France

Hopital Curie; 🇫🇷 Paris, France

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

Asklepios Kliniken Hamburg GmbH; 🇩🇪 Hamburg, Germany

Deutsches Krebsforschungszentrum; 🇩🇪 Heidelberg, Germany

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Sheba Medical Center; 🇮🇱 Tel Aviv, Israel

Ospedale San Raffaele; 🇮🇹 Milano, Italy

Niguarda Cancer Centre; 🇮🇹 Milan, Italy

Istituti Fisioterapici Ospitalieri; 🇮🇹 Roma, Italy

National Cancer Center Hospital; 🇯🇵 Chuo-Ku, Japan

St. Marianna University School of Medicine Hospital; 🇯🇵 Kawasaki, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

National Cancer Center East; 🇯🇵 Tokyo, Japan

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital- Yonsei Cancer Center; 🇰🇷 Seoul, Korea, Republic of

NKI; 🇳🇱 Amsterdam, Netherlands

Amsterdam Medical Center; 🇳🇱 Amsterdam, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

University Hospital Oslo; 🇳🇴 Oslo, Norway

National Cancer Centre of Singapore PTE LTD; 🇸🇬 Singapore, Singapore

Vall D'Hebron Institute of Oncology (VHIO); 🇪🇸 Barcelona, Spain

START Hospital Fundación Jiménez Diaz; 🇪🇸 Madrid, Spain

START Hospital Universitario Madrid Sanchinarro; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Clínica Universidad de Navarra; 🇪🇸 Pamplona, Spain

Instituto Valenciano Oncologia; 🇪🇸 Valencia, Spain

Karolinska Universitetssjukhuset; 🇸🇪 Solna, Sweden

National Taiwan University Hospital 7; 🇨🇳 Taipei, Taiwan

Sarah Cannon Research Institute; 🇬🇧 London, United Kingdom