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Trial record 1 of 1 for:    NCT02912949
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A Study of MCLA-128 in Patients With Solid Tumors Harboring an NRG1 Fusion

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ClinicalTrials.gov Identifier: NCT02912949
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : August 16, 2019
Sponsor:
Information provided by (Responsible Party):
Merus N.V.

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 MCLA-128 in patients with solid tumors harboring an NRG1 fusion.

Condition or disease Intervention/treatment Phase
Solid Tumours Harboring NRG1 Fusion NSCLC Harboring NRG1 Fusion Pancreatic Cancer Harboring NRG1 Fusion NRG1 Fusion Drug: MCLA-128 Phase 1 Phase 2

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 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 Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 2015
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 2 Pancreatic cancer harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of MCLA-128 (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific

Experimental: Part 2 NSCLC cancer harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of MCLA-128 (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific

Experimental: Part 2 Solid tumour (basket) harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of MCLA-128 (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific




Primary Outcome Measures :
  1. Characterize the safety and tolerability of MCLA-128 [ Time Frame: 6-12 months ]
    Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)

  2. Objective overall response rate (ORR) [ Time Frame: 36 months ]
    Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)

  3. Duration of response (DOR) [ Time Frame: 36 months ]
    Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)

  4. Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
    Evaluate the correlation between the anti-tumor activity of MCLA-128 and HER2

  5. Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
    Evaluate the correlation between the anti-tumor activity of MCLA-128 and HER3

  6. Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
    Evaluate the correlation between the anti-tumor activity of MCLA-128 and Heregulin

  7. Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
    Evaluate the correlation between the anti-tumor activity of MCLA-128 and disease related biomarkers (i.e. CA19-9)


Secondary Outcome Measures :
  1. Incidence of AE [safety and tolerability] [ Time Frame: 36 months ]
    Evaluate severity, frequency and duration of Adverse events

  2. Maximum plasma concentration [Cmax] [ Time Frame: 36 months ]
    Assess the Cmax of MCLA-128

  3. Volume of distribution [V] [ Time Frame: 36 months ]
    Assess the volume of distribution of MCLA-128

  4. Volume of distribution at steady state [Vss] [ Time Frame: 36 months ]
    Assess the volume of distribution of MCLA-128 at steady state

  5. half-life [t1/2] [ Time Frame: 36 months ]
    Assess the half-life of MCLA-128

  6. Area under the concentration versus time curve from time zero to time t [AUC0-t] [ Time Frame: 36 months ]
    Assess the Area under the concentration versus time curve from time zero to time t [AUC0-t] of MCLA-128

  7. area under the concentration versus time curve [AUC0-∞] [ Time Frame: 36 months ]
    Assess the area under the concentration versus time curve [AUC0-∞] of MCLA-128

  8. time to reach maximum concentration [tmax] [ Time Frame: 36 months ]
    Assess the time to reach maximum concentration [tmax] of MCLA-128

  9. Incidence of anti-drug antibodies against MCLA-128 [ Time Frame: 36 months ]
    Assess the Incidence of anti-drug antibodies against MCLA-128

  10. serum titers of anti-drug antibodies [ Time Frame: 36 months ]
    Assess serum titers of anti-drug antibodies

  11. Anti-tumor response of MCLA-128 by RECIST v1.1 [ Time Frame: 36 months ]
    Assess the anti-tumor response of MCLA-128 by RECIST v1.1

  12. Clinical Benefit Rate (CBR) of MCLA-128 [ Time Frame: 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 12 weeks) by RECIST v1.1 .

  13. Progression Free Survival (PFS) and survival [ Time Frame: 36 months ]
    Evaluation of clinical benefit assessed by RECIST v1.1 determining objective progression-free survival (PFS) and/or survival



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02912949


Contacts
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Contact: Ernesto Wasserman, MD +31 85 016 2500 enquiries@merus.nl
Contact: Andres Sirulnik, MD PhD +31 85 016 2500 enquiries@merus.nl

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Sponsors and Collaborators
Merus N.V.
Investigators
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Study Director: Medical Director: Ernesto Wasserman, MD Merus N.V.

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Responsible Party: Merus N.V.
ClinicalTrials.gov Identifier: NCT02912949     History of Changes
Other Study ID Numbers: MCLA-128-CL01
2014-003277-42 ( EudraCT Number )
First Posted: September 23, 2016    Key Record Dates
Last Update Posted: August 16, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merus N.V.:
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
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Immunoglobulins
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs