Clinical Trials /

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

NCT02912949

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MCLA-128-CL01
  • SECONDARY ID: 2014-003277-42
  • NCT ID: NCT02912949

Conditions

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

Interventions

DrugSynonymsArms
zenocutuzumab (MCLA-128)bispecificPart 2 NSCLC cancer harboring NRG1 fusion

Purpose

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.

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 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 25 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 Arms

NameTypeDescriptionInterventions
Part 2 Pancreatic cancer harboring NRG1 fusionExperimentalParticipants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
  • zenocutuzumab (MCLA-128)
Part 2 NSCLC cancer harboring NRG1 fusionExperimentalParticipants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
  • zenocutuzumab (MCLA-128)
Part 2 Solid tumour (basket) harboring NRG1 fusionExperimentalParticipants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
  • zenocutuzumab (MCLA-128)

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 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:

               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;

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Characterize the safety and tolerability of zenocutuzumab (MCLA-128)
Time Frame:6-12 months
Safety Issue:
Description:Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)

Secondary Outcome Measures

Measure:Incidence of AE [safety and tolerability]
Time Frame:36 months
Safety Issue:
Description:Evaluate severity, frequency and duration of Adverse events
Measure:Maximum plasma concentration [Cmax]
Time Frame:36 months
Safety Issue:
Description:Assess the Cmax of zenocutuzumab (MCLA-128)
Measure:Volume of distribution [V]
Time Frame:36 months
Safety Issue:
Description:Assess the volume of distribution of zenocutuzumab (MCLA-128)
Measure:Volume of distribution at steady state [Vss]
Time Frame:36 months
Safety Issue:
Description:Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state
Measure:half-life [t1/2]
Time Frame:36 months
Safety Issue:
Description:Assess the half-life of zenocutuzumab (MCLA-128)
Measure:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame:36 months
Safety Issue:
Description:Assess the Area under the concentration versus time curve from time zero to time t [AUC0-t] of zenocutuzumab (MCLA-128)
Measure:area under the concentration versus time curve [AUC0-∞]
Time Frame:36 months
Safety Issue:
Description:Assess the area under the concentration versus time curve [AUC0-∞] of zenocutuzumab (MCLA-128)
Measure:time to reach maximum concentration [tmax]
Time Frame:36 months
Safety Issue:
Description:Assess the time to reach maximum concentration [tmax] of zenocutuzumab (MCLA-128)
Measure:Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
Time Frame:36 months
Safety Issue:
Description:Assess the Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
Measure:serum titers of anti-drug antibodies
Time Frame:36 months
Safety Issue:
Description:Assess serum titers of anti-drug antibodies
Measure:Anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1
Time Frame:36 months
Safety Issue:
Description:Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1
Measure:Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128)
Time Frame:36 months
Safety Issue:
Description: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 12 weeks) by RECIST v1.1 .
Measure:Progression Free Survival (PFS) and survival
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining objective progression-free survival (PFS) and/or survival

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merus N.V.

Trial Keywords

  • 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

Last Updated

January 23, 2020