Clinical Trials /

A Study of MCLA-128 in Patients With Solid Tumors

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 MCLA-128

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Gastric Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MCLA-128 in Patients With Solid Tumors
  • 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

  • Malignant Solid Tumour
  • Breast Cancer
  • Gastric Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
MCLA-128bispecificPart 1 Dose Escalation

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 MCLA-128

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 consists of 2 parts. Part 1 is a dose escalation
      and Part 2 is a dose expansion cohort. Part 1 has been completed.

      Part 2 patient populations of interest to receive the RP2D determined in Part 1 are:

        -  relapsed/refractory HER2-amplified breast cancer (Group A);

        -  advanced/metastatic epithelial ovarian cancer (Group C);

        -  advanced/metastatic HER2-amplified gastric cancer or esophageal-gastric junction
           adenocarcinoma (Group D); .

        -  advanced/metastatic endometrial cancer (Group E);

        -  advanced/metastatic or recurring HER2 expressing non small cell lung cancer (Group F);

      Part 2 will further characterize the safety and tolerability of the selected dose level of
      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).

      The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of
      study drug); Treatment period (first dose of study drug until the last dose of study drug
      with treatment cycles of 21 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 10 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 1 Dose EscalationExperimentalCohorts receiving escalating doses of MCLA-128 until MTD or RP2D is reached. Each Cycle is 21 days. Single agent treatment.
  • MCLA-128
Part 2 breast cancerExperimentalParticipants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
  • MCLA-128
Part 2 ovarian cancerExperimentalParticipants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
  • MCLA-128
Part 2 gastric/GE junction cancerExperimentalParticipants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
  • MCLA-128
Part 2 endometrial cancerExperimentalParticipants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
  • MCLA-128
Part 2 non small cell lung cancerExperimentalParticipants will receive intravenous infusion of MCLA-128 at the recommended Phase 2 dose (RP2D) once per cycle. The duration of each treatment cycle is 21 days.
  • MCLA-128

Eligibility Criteria

        Inclusion Criteria:

          -  At least one measurable lesion according to RECIST v1.1;

          -  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;

          -  At least a 4-week interval since last received radiotherapy;

          -  Recovery from major surgery;

          -  Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support;

          -  Platelets ≥100 x 109/L;

          -  Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent);

          -  Total bilirubin <1.5 times the upper limit of normal (ULN);

          -  AST (SGOT) ≤2.5 x ULN; ALT (SGPT) ≤2.5 x ULN; ≤5 x ULN for patients with advanced
             solid tumors with liver metastases; patients with confirmed bony metastases will be
             permitted on study with isolated elevations in ALP >5 x ULN;

          -  Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of >50
             mL/min

          -  coagulation function (INR, and aPTT ≤1.5 x ULN , unless on therapeutic
             anticoagulants);

          -  Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine

          -  Able to provide a tumor biopsy sample (preferably fresh or else archival); if
             archival: taken within 2 years from screening;

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception during and for 6 month after
             completion of study therapy;

          -  Patient with metastatic cancer who has disease progression after having received
             treatment with all available therapies known to convey clinical benefit

        Specific Inclusion Criteria for Part 2 (Group A) breast cancer (BC):

          -  Histologically-confirmed and documented advanced / metastatic BC, relapsed/refractory
             to at least 2 prior HER2 directed regimen for BC;

          -  Confirmed HER2 amplification based on historical pathology report or analysis of
             baseline fresh/archival tumor sample.

        Specific Inclusion Criteria for Part 2 (Group C) ovarian cancer (OC):

          -  Histologically-confirmed and documented advanced/metastatic epithelial OC for which no
             curative therapy is available;

          -  Prior therapy including all available standard therapies and at least 1 platinum based
             chemotherapy.

        Specific Inclusion Criteria for Part 2 (Group D) gastric or esophageal-gastric junction
        cancer (GC or GEC):

          -  Histologically-confirmed and documented advanced/metastatic GC or GEC ;

          -  Prior chemotherapy including platinum and fluoropyrimidine based treatment and
             trastuzumab

          -  Confirmed HER2 amplification based on historical pathology report or analysis of
             fresh/archival tumor sample.

        Specific Inclusion Criteria for Part 2 (Group E) endometrial cancer (EC):

          -  Histologically-confirmed and documented advanced/metastatic EC for which no curative
             therapy is available;

          -  Prior therapy including all available standard therapies and at least 1 prior
             chemotherapy.

        Specific Inclusion Criteria for Part 2 (Group F) Non small cell lung cancer (NSCLC):

          -  Histologically or cytologically documented diagnosis of Stage IIIB not amenable to
             radical treatment or Stage IV NSCLC; with pathological characterization of
             non-squamous or squamous histological subtype and adenocarcinoma subtype
             classification;

          -  Confirmed HER2 expression (by IHC) based on historical pathology report or analysis of
             baseline (fresh or archival) tumor sample;

          -  Prior treatment included all available standard therapies with at least one regimen of
             platinum-based chemotherapy in locally advanced/metastatic setting/recurrent NSCLC
             with documented disease progression by investigator assessment;

          -  Patients with ALK fusion oncogene with documented disease progression or intolerance
             with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of
             ALK fusion oncogene NSCLC;

          -  Patients with known mutation in the EGFR gene must have documented disease progression
             or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC.

        Exclusion Criteria:

          -  Pregnant or lactating;

          -  Presence of an active infection or an unexplained fever;

          -  Known hypersensitivity to any of the components of MCLA-128;

          -  Known HIV, Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have
             undetectable viral loads are eligible

          -  Any untreated central nervous system lesion

          -  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.

          -  Prior anti-tumor therapy within 28 days prior to the first scheduled day of dosing
             with MCLA-128 unless a time interval equal to at least five half-lives of the
             investigational agent has passed;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose Limiting Toxicities (DLT)
Time Frame:6-12 months
Safety Issue:
Description:Evaluation of number of participants with treatment related toxicities observed during the dose escalation.

Secondary Outcome Measures

Measure:Incidence of Treatment Related AE [safety and tolerability]
Time Frame:36 months
Safety Issue:
Description:Frequency of Treatment Related AEs or SAEs
Measure:Maximum plasma concentration [Cmax]
Time Frame:36 months
Safety Issue:
Description:Maximum plasma concentration [Cmax] as measured from all individual plasma concentrations
Measure:Volume of distribution [V]
Time Frame:36 months
Safety Issue:
Description:volume of distribution [V]
Measure:Volume of distribution at steady state [Vss]
Time Frame:36 months
Safety Issue:
Description:volume of distribution at steady state [Vss]
Measure:half-life [t1/2]
Time Frame:36 months
Safety Issue:
Description:half-life [t1/2]
Measure:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame:36 months
Safety Issue:
Description:area under the concentration versus time curve from time zero to time t [AUC0-t]
Measure:area under the concentration versus time curve [AUC0-∞]
Time Frame:36 months
Safety Issue:
Description:area under the concentration versus time curve [AUC0-∞]
Measure:time to reach maximum concentration [tmax]
Time Frame:36 months
Safety Issue:
Description:time to reach maximum concentration [tmax]
Measure:Incidence of anti-drug antibodies against MCLA-128
Time Frame:36 months
Safety Issue:
Description:Number of participants with anti-drug antibodies against MCLA-128
Measure:serum titers of anti-drug antibodies
Time Frame:36 months
Safety Issue:
Description:serum titers of anti-drug antibodies against MCLA-128
Measure:Anti-tumor response of MCLA-128 by RECIST v1.1
Time Frame:36 months
Safety Issue:
Description:Anti-tumor response as measured by RECIST v1.1
Measure:Clinical Benefit Rate (CBR) of 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:Objective overall response rate (ORR)
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Measure:Duration of response (DOR)
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)
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
  • First-in-human
  • MCLA-128
  • Antibodies, Bispecific
  • Immunologic Factors
  • Cytokines

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