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

NRG1 Fusion Clinical Trial

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 (eNRGy)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02912949
• Other study ID #: MCLA-128-CL01
• Secondary ID: 2014-003277-42
• Status: Recruiting
• Phase: Phase 2
• Start date: January 2015
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: Merus N.V.
• Contact: Merus Inquiries
• Phone: 1-833-NRG-1234
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 examined:

• Group F: Patients with NSCLC with documented NRG1 fusion

• Group G: Patients with pancreatic adenocarcinoma 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. >14 days or >5 half-lives prior to study entry, whichever is shorter.

2. >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 >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 <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's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Related Conditions & MeSH terms

• NRG1 Fusion
• NSCLC Harboring NRG1 Fusion
• Pancreatic Cancer Harboring NRG1 Fusion
• Pancreatic Neoplasms
• Solid Tumours Harboring NRG1 Fusion

Intervention

Drug:
• zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3

Locations

Country	Name	City	State
Austria	Salzburger Universitatsklinikum	Salzburg
Belgium	UZ Leuven	Leuven
Canada	Princess MargaretCancer Centre	Toronto	Ontario
Denmark	Rigshospitalet	Copenhagen
France	Centre Leon Berard	Lyon
France	Hospital Louis Pradel, FR	Lyon
France	Hopital Cochin	Paris
France	Hopital Curie	Paris
France	Institut Gustave Roussy	Paris
Germany	Asklepios Klinik Altona	Hamburg
Germany	Asklepios Kliniken Hamburg GmbH	Hamburg
Germany	Deutsches Krebsforschungszentrum	Heidelberg
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sheba Medical Center	Tel Aviv
Italy	Niguarda Cancer Centre	Milan
Italy	Ospedale San Raffaele	Milano
Italy	Istituti Fisioterapici Ospitalieri	Roma
Japan	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
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University College of Medicine	Seoul
Korea, Republic of	Severance Hospital- Yonsei Cancer Center	Seoul
Netherlands	Amsterdam Medical Center	Amsterdam
Netherlands	NKI	Amsterdam
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	UMC Utrecht	Utrecht
Norway	University Hospital Oslo	Oslo
Singapore	National Cancer Centre of Singapore PTE LTD	Singapore
Spain	Vall D'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	START Hospital Fundación Jiménez Diaz	Madrid
Spain	START Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Instituto Valenciano Oncologia	Valencia
Sweden	Karolinska Universitetssjukhuset	Solna
Taiwan	National Taiwan University Hospital 7	Taipei
United Kingdom	Sarah Cannon Research Institute	London
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Dana Farber Cancer Center	Boston	Massachusetts
United States	St. James Healthcare	Butte	Montana
United States	The Oncology Institute of Hope and Innovation	Cerritos	California
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Hematology-Oncology Specialist of Fredericksburg	Fredericksburg	Virginia
United States	Memorial Cancer Institute	Hollywood	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California Irvine	Irvine	California
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Northwest Oncology & Hematology	Rolling Meadows	Illinois
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Sharp Memorial Hospital	San Diego	California
United States	Virginia Mason Hospital & Seattle Medical Center	Seattle	Washington
United States	Averra Medical Group	Sioux Falls	South Dakota
United States	Hematology Oncology Associates	Spokane	Washington
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merus N.V.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective overall response rate (ORR) as per local investigator's assessment	Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)	36 months
Primary	Duration of response per RECIST v1.1 as per local Investigator's assessment.	To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally	36 Months
Secondary	Overall response rate as per central review	Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1 as assessed centrally	36 months
Secondary	Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and centrally	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 .	36 months
Secondary	Duration of Response as per central review	To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed centrally	36 months
Secondary	Time to response per RECIST v1.1. as per local Investigator's assessment.	To assess time to onset of response in patients with NRG1 fusions as assessed locally	36 months
Secondary	Time to response per RECIST v1.1. as per central review	To assess time to onset of response in patients with NRG1 fusions as assessed centrally	36 months
Secondary	Characterize the safety and tolerability of zenocutuzumab (MCLA-128)	Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)	6-12 months
Secondary	Maximum plasma concentration [Cmax]	Assess the Cmax of zenocutuzumab (MCLA-128)	36 months
Secondary	Volume of distribution [V]	Assess the volume of distribution of zenocutuzumab (MCLA-128)	36 months
Secondary	Volume of distribution at steady state [Vss]	Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state	36 months
Secondary	Area under the concentration versus time curve from time zero to time t [AUC0-t]	Assess the Area under the concentration versus time curve from time zero to time t [AUC0-t] of zenocutuzumab (MCLA-128)	36 months
Secondary	half-life [t1/2]	Assess the half-life of zenocutuzumab (MCLA-128)	36 months
Secondary	area under the concentration versus time curve [AUC0-8]	Assess the area under the concentration versus time curve [AUC0-8] of zenocutuzumab (MCLA-128)	36 months
Secondary	time to reach maximum concentration [tmax]	Assess the time to reach maximum concentration [tmax] of zenocutuzumab (MCLA-128)	36 months
Secondary	Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)	Assess the Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)	36 months
Secondary	serum titers of anti-drug antibodies	Assess serum titers of anti-drug antibodies	36 months
Secondary	Evaluation of progression free survival (PFS)		36 months
Secondary	Evaluation of overall survival (OS)		12 months

External Links

•   For more information about MCLA-128 and the MCLA-128-CL01 study