Clinical Trials /

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

NCT04868877

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: MCLA-129-CL01
  • NCT ID: NCT04868877

Conditions

  • Non-Small Cell Lung Cancer Metastatic
  • Gastric Cancer
  • Head and Neck Cancer

Interventions

DrugSynonymsArms
MCLA-129MCLA-129

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
MCLA-129Experimental
  • MCLA-129

Eligibility Criteria

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

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To evaluate preliminary antitumor activity in terms of best overall response (BOR)
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:To evaluate preliminary antitumor activity in terms of overall response rate (ORR)
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:To evaluate preliminary antitumor activity in terms of disease control rate (DCR)
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:To evaluate preliminary antitumor activity in terms of duration of response (DoR).
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:To evaluate progression-free survival (PFS)
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:To evaluate overall survival (OS).
Time Frame:Every 8 weeks until study ends, approximately 2 years
Safety Issue:
Description:
Measure:Maximum plasma concentration [Cmax]
Time Frame:12 months
Safety Issue:
Description:
Measure:Plasma concentration at 0 hours [C0h]
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the concentration versus time curve [AUC0-∞]
Time Frame:12 months
Safety Issue:
Description:
Measure:Time to reach maximum concentration [tmax]
Time Frame:12 months
Safety Issue:
Description:
Measure:Half-life [t1/2]
Time Frame:12 months
Safety Issue:
Description:
Measure:To assess changes in cytokines (TNFα) in serum blood following administration of MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:To assess changes in cytokines (IFNγ) in serum blood following administration of MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:To assess changes in cytokines (IL-1β) in serum blood following administration of MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:To assess changes in cytokines (IL-2) in serum blood following administration of MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:To assess changes in cytokines (IL-6) in serum blood following administration of MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:Incidence of anti-drug antibodies in serum blood against MCLA-129
Time Frame:12 months
Safety Issue:
Description:
Measure:Serum titers of anti-drug (MCLA-129) antibodies in serum blood
Time Frame:12 months
Safety Issue:
Description:

Details

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

Trial Keywords

  • MCLA-129
  • EGFR inhibitor
  • NSCLC

Last Updated

May 24, 2021