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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 9, 2023
Sponsor:
Information provided by (Responsible Party):
Merus N.V.

Study Description
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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, HNSCC, GC/GEJ, ESCC, or other solid tumors and who have progressed after receiving prior therapy for advanced/metastatic disease.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Metastatic Gastric Cancer Esophageal Squamous Cell Carcinoma Head and Neck Squamous Cell Carcinoma Drug: MCLA-129 Drug: Osimertinib Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 28, 2021
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 2 NSCLC harboring EGFR exon 20 Insertion
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
 Drug: MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Other Name: bispecific
Experimental: Part 2 NSCLC harboring cMet exon 14 skipping mutation
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
 Drug: MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Other Name: bispecific
Experimental: Part 2 Select solid tumors harboring an EGFR or cMet driving mutation
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
 Drug: MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Other Name: bispecific
Experimental: Part 2 NSCLC First-line
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.
 Drug: MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Other Name: bispecific

Drug: Osimertinib
Approved, 3rd-generation EGFR-TKI
Other Name: Tagrisso
Experimental: Part 2 NSCLC Second-line or more
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.
 Drug: MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Other Name: bispecific

Drug: Osimertinib
Approved, 3rd-generation EGFR-TKI
Other Name: Tagrisso


Outcome Measures
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Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single agent MCLA-129 in patients with NSCLC, GC/GEJ adenocarcinoma, HNSCC or ESCC, with disease progression after prior therapy for advanced/metastatic disease. [ Time Frame: First 28 days of treatment ]
  2. To evaluate the ORR of MCLA-129 alone or in combination with Osimertinib in molecularly defined populations of advanced/metastatic solid tumors. [ Time Frame: From first dose until 1 year after end of treatment or initiation of an alternative treatment, whichever occurs first. ]

Secondary Outcome Measures :
  1. To evaluate preliminary antitumor activity in terms of best overall response (BOR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  2. To evaluate preliminary antitumor activity in terms of overall response rate (ORR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  3. To evaluate preliminary antitumor activity in terms of disease control rate (DCR) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  4. To evaluate preliminary antitumor activity in terms of duration of response (DoR). [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  5. To evaluate progression-free survival (PFS) [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  6. To evaluate overall survival (OS). [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
  7. Maximum plasma concentration [Cmax] [ Time Frame: 12 months ]
  8. Plasma concentration at 0 hours [C0h] [ Time Frame: 12 months ]
  9. Area under the concentration versus time curve from time zero to time t [AUC0-t] [ Time Frame: 12 months ]
  10. Area under the concentration versus time curve [AUC0-∞] [ Time Frame: 12 months ]
  11. Time to reach maximum concentration [tmax] [ Time Frame: 12 months ]
  12. Half-life [t1/2] [ Time Frame: 12 months ]
  13. To assess changes in cytokines (TNFα) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  14. To assess changes in cytokines (IFNγ) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  15. To assess changes in cytokines (IL-1β) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  16. To assess changes in cytokines (IL-2) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  17. To assess changes in cytokines (IL-6) in serum blood following administration of MCLA-129 [ Time Frame: 12 months ]
  18. Incidence of anti-drug antibodies in serum blood against MCLA-129 [ Time Frame: 12 months ]
  19. Serum titers of anti-drug (MCLA-129) antibodies in serum blood [ Time Frame: 12 months ]
  20. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 12 months ]
  21. Proportion of patient with treatment discontinuations [ Time Frame: 12 months ]

Eligibility Criteria
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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:

  • Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced unresected disease that is incurable.
  • Patients with NSCLC, GC/GEJ, HNSCC, or ESCC 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.
  • Part Two: Patients with NSCLC, HNSCC, other solid tumors and applicable mutations as determined by the investigator
  • 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 10^9/L
    • Hemoglobin ≥9 g/dL
    • Platelets ≥100 x 10^9/L
    • Corrected total serum calcium within normal ranges
    • Serum magnesium within normal ranges (or corrected with supplements)
    • Serum potassium within normal ranges
    • 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.
  • 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. Patients who received prior radiotherapy to ≥25% of bone marrow at any time are not eligible.
  • 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) or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities. Patients with cardiac pacemakers who are clinically stable are eligible.
    • Heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
    • 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 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).
Contacts and Locations
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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): NCT04868877


Contacts
Layout table for location contacts
Contact: Merus Inquiries 617-401-4499 USenquiries@merus.nl

Locations
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Sponsors and Collaborators
Merus N.V.
More Information
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Responsible Party: Merus N.V.
ClinicalTrials.gov Identifier: NCT04868877    
Other Study ID Numbers: MCLA-129-CL01
First Posted: May 3, 2021    Key Record Dates
Last Update Posted: May 9, 2023
Last Verified: May 2023

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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.:
MCLA-129
EGFR inhibitor
NSCLC
 C-MET
GC/GEJ
Head and Neck Cancer
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
 Digestive System Diseases
Gastrointestinal Diseases
Head and Neck Neoplasms
Esophageal Neoplasms
Esophageal Diseases
Osimertinib
Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents