Clinical trial NCT02912949: A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Solid Tumours Harboring NRG1 Fusion
NSCLC Harboring NRG1 Fusion
Pancreatic Cancer Harboring NRG1 Fusion
NRG1 Fusion
Keywords: Bispecific Antibody IgG1, HER2, HER3
MCLA-128
Antibodies, Bispecific
Immunologic Factors
NRG1 fusion
Solid tumor
Pancreatic cancer
PDAC
Non-small cell lung cancer
NSCLC
zenocutuzumab
Lead sponsor: Partner Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-23
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Objective overall response rate (ORR) as per local investigator's assessment
timeFrame: 36 months
measure: Duration of response per RECIST v1.1 as per local Investigator's assessment.
timeFrame: 36 Months
Secondary outcomes:
measure: Overall response rate as per Blinded Independent Central Review (BICR)
timeFrame: 36 months
measure: Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and BICR
timeFrame: 36 months
measure: Duration of Response as per BICR
timeFrame: 36 months
measure: Time to response per RECIST v1.1. as per local investigator assessment
timeFrame: 36 months
measure: Time to response per RECIST v1.1. as per BICR
timeFrame: 36 months
measure: Characterize the safety and tolerability of zenocutuzumab (MCLA-128)
timeFrame: 6-12 months
measure: Maximum plasma concentration [Cmax]
timeFrame: 36 months
measure: Volume of distribution [V]
timeFrame: 36 months
measure: Volume of distribution at steady state [Vss]
timeFrame: 36 months
measure: Area under the concentration versus time curve from time zero to time t [AUC0-t]
timeFrame: 36 months
measure: half-life [t1/2]
timeFrame: 36 months
measure: area under the concentration versus time curve [AUC0-∞]
timeFrame: 36 months
measure: time to reach maximum concentration [tmax]
timeFrame: 36 months
measure: Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
timeFrame: 36 months
measure: serum titers of anti-drug antibodies
timeFrame: 36 months
measure: Evaluation of progression free survival (PFS)
timeFrame: 36 months
measure: Evaluation of overall survival (OS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Cerritos
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: District of columbia
country: United States
facility: Georgetown University
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Rolling Meadows
country: United States
facility: Northwest Oncology & Hematology
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare
state: Montana
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Averra Medical Group
state: South Dakota
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fredericksburg
country: United States
facility: Hematology-Oncology Specialist of Fredericksburg
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Hospital & Seattle Medical Center
state: Washington
city: Spokane
country: United States
facility: Hematology Oncology Associates
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Salzburg
country: Austria
facility: Salzburger Universitatsklinikum
city: Leuven
country: Belgium
facility: UZ Leuven
city: Toronto
country: Canada
facility: Princess MargaretCancer Centre
state: Ontario
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Hospital Louis Pradel, FR
city: Paris
country: France
facility: Institut Gustave Roussy
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Curie
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg GmbH
city: Heidelberg
country: Germany
facility: Deutsches Krebsforschungszentrum
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Tel Aviv
country: Israel
facility: Sheba Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milan
country: Italy
facility: Niguarda Cancer Centre
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: National Cancer Center East
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Severance Hospital- Yonsei Cancer Center
city: Amsterdam
country: Netherlands
facility: NKI
city: Amsterdam
country: Netherlands
facility: Amsterdam Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Oslo
country: Norway
facility: University Hospital Oslo
city: Singapore
country: Singapore
facility: National Cancer Centre of Singapore PTE LTD
city: Barcelona
country: Spain
facility: Vall D'Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: START Hospital Fundación Jiménez Diaz
city: Madrid
country: Spain
facility: START Hospital Universitario Madrid Sanchinarro
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital 7
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
Study officials:
affiliation: Memorial Sloan Kettering Medical Center
name: Alison Schram, MD
role: PRINCIPAL_INVESTIGATOR
References: