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A Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors

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ClinicalTrials.gov Identifier: NCT04868877
Recruitment Status : Recruiting
First Posted : May 3, 2021
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Merus N.V.

Tracking Information
First Submitted Date  ICMJE April 9, 2021
First Posted Date  ICMJE May 3, 2021
Last Update Posted Date May 24, 2021
Actual Study Start Date  ICMJE April 28, 2021
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2021)
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single agent MCLA-129 in patients with NSCLC, HNSCC or other solid tumors, with disease progression after prior therapy for advanced/metastatic disease. [ Time Frame: First 28 days of treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2021)
  • To evaluate preliminary antitumor activity in terms of best overall response (BOR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • To evaluate preliminary antitumor activity in terms of overall response rate (ORR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • To evaluate preliminary antitumor activity in terms of disease control rate (DCR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • To evaluate preliminary antitumor activity in terms of duration of response (DoR). [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • To evaluate progression-free survival (PFS) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • To evaluate overall survival (OS). [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  • Maximum plasma concentration [Cmax] [ Time Frame: 12 months ]
  • Plasma concentration at 0 hours [C0h] [ Time Frame: 12 months ]
  • Area under the concentration versus time curve from time zero to time t [AUC0-t] [ Time Frame: 12 months ]
  • Area under the concentration versus time curve [AUC0-∞] [ Time Frame: 12 months ]
  • Time to reach maximum concentration [tmax] [ Time Frame: 12 months ]
  • Half-life [t1/2] [ Time Frame: 12 months ]
  • To assess changes in cytokines (TNFα) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  • To assess changes in cytokines (IFNγ) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  • To assess changes in cytokines (IL-1β) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  • To assess changes in cytokines (IL-2) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  • To assess changes in cytokines (IL-6) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  • Incidence of anti-drug antibodies in serum blood against MCLA-129 [ Time Frame: 12 months ]
  • Serum titers of anti-drug (MCLA-129) antibodies in serum blood [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors
Official Title  ICMJE Phase 1/2 Dose Escalation and Expansion Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors
Brief Summary A phase 1/2 open-label multicenter study will be performed with an initial dose escalation part to determine the MTD and/or the RP2D of MCLA-129 as monotherapy in patients with NSCLC, or HNSCC or other solid tumors and who have progressed after receiving prior therapy for advanced/metastatic disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer Metastatic
  • Gastric Cancer
  • Head and Neck Cancer
Intervention  ICMJE Drug: MCLA-129
In the dose escalation phase 1 part, MCLA-129 will be administered every two weeks with increasing doses to patients with NSCLC or patients with HNSCC, or other solid tumors, who in all cases, have progressed after receiving prior therapy for advanced/metastatic disease. In Part 2, patients with NSCLC and other advanced solid tumors will be dosed with MCLA-129 every two weeks at the RP2D.
Study Arms  ICMJE Experimental: MCLA-129
Intervention: Drug: MCLA-129
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 27, 2021)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2025
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced unresected disease that is incurable.
  • Patients with NSCLC or other solid tumors who have failed prior standard first-line treatment. Patients must have progressed on or be intolerant to therapies that are known to provide clinical benefit. There is no limit to the number of prior treatment regimens.
  • Availability of archival or a fresh tumor tissue sample.
  • Measurable disease as defined by RECIST version 1.1 by radiologic methods.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy ≥ 12 weeks, as per Investigator.
  • Adequate organ function:

    • Absolute neutrophil count (ANC) ≥1.5 X 109/L
    • Hemoglobin ≥9 g/dL
    • Platelets ≥100 x 109/L
    • Corrected total serum calcium within normal ranges
    • Serum magnesium within normal ranges (or corrected with supplements)
    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN (patients with Gilbert's syndrome are eligible if conjugated bilirubin value is within normal limits); in cases of liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed
    • Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min calculated according to the Cockcroft and Gault formula or MDRD formula for patients aged >65 years
    • Serum albumin >3.3 g/dL

Exclusion Criteria:

  • Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy (> 10 mg prednisone or equivalent) to control symptoms within 14 days of study entry.
  • Known leptomeningeal involvement.
  • Participation in another clinical study or treatment with any investigational drug within 4 weeks prior to study entry.
  • Prior treatment with a bispecific EGFR-c-MET antibody.
  • Systemic anticancer therapy or immunotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of study drug. For cytotoxic agents that have major delayed toxicity (e.g., mitomycin C, nitrosoureas), a washout period of 6 weeks is required.
  • Major surgery or radiotherapy within 3 weeks of the first dose of study drug.
  • Persistent grade >1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 NCI-CTCAE v5.0 and hypothyroidism ≤ grade 2 which is stable on hormone replacement are allowed.
  • History of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents.
  • History of clinically significant cardiovascular disease including, but not limited to:

    • Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to first dose of study drug, or any of the following within 6 months prior to the first dose of study drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome.
    • Prolonged QT interval > 480 msec or clinically significant cardiac arrythmia or electrophysiologic disease (i.e., placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). Patients with cardiac pacemakers who are clinically stable are eligible.
    • Uncontrolled (persistent) arterial hypertension: systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 100 mm Hg.
    • Congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF within 6 months of the first dose of study drug.
    • Clinically significant pericardial effusion.
    • Myocarditis.
  • History of interstitial lung disease including drug-induced interstitial lung disease, radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year.
  • Previous or concurrent malignancy, excluding non-basal cell carcinomas of skin or carcinoma in situ of the uterine cervix, unless the tumor was treated with curative or palliative intent and in the opinion of the Investigator, with Sponsor agreement, the previous or concurrent malignancy condition does not affect the assessment of safety and efficacy of the study drug.
  • Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy.
  • Current serious illness or medical conditions including, but not limited to uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
  • Active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment.
  • Positive test for Hepatitis C ribonucleic acid (HCV RNA);
  • Known history of HIV (HIV 1/2 antibodies).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Merus Inquiries 617-401-4499 USenquiries@merus.nl
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04868877
Other Study ID Numbers  ICMJE MCLA-129-CL01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merus N.V.
Study Sponsor  ICMJE Merus N.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merus N.V.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP