Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in Combination
- Conditions
- Non-Small Cell Lung Cancer MetastaticColorectal CancerEsophageal Squamous Cell CarcinomaHead and Neck Squamous Cell CarcinomaGastric Cancer
- Interventions
- Registration Number
- NCT04868877
- Lead Sponsor
- Merus N.V.
- 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 in monotherapy or in combination in patients with NSCLC, HNSCC, GC/GEJ, ESCC, or other solid tumors and who are treatment naïve or have progressed after receiving prior therapy for advanced/metastatic disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 576
Not provided
- 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 hypersensitivity reaction or any toxicity attributed to chemotherapy and components.
- History of clinically significant cardiovascular disease
- Past medical history of ILD or pneumonitis, or any evidence of clinically active ILD or pneumonitis.
- 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 without receiving antiviral treatment.
- Positive test for Hepatitis C
- Known history of HIV (HIV 1/2 antibodies). Patients with HIV with undetectable viral load are allowed. In
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutation MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D). Part 2 NSCLC Second-line or more harboring EGFR exon 20 Insertion MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D). Part 2 NSCLC First-line harboring EGFR sensitizing mutations MCLA-129 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. Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy) Chemotherapy Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance. Part 2 NSCLC First-line harboring EGFR sensitizing mutations Osimertinib 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. Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy) Chemotherapy Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance. Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib) Osimertinib 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. Part 2 Selected solid tumors with or without an EGFR or cMet alteration MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D). Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib) MCLA-129 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. Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy) MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance. Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy) MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance.
- Primary Outcome Measures
Name Time Method To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) First 28 days of treatment To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single-agent MCLA-129 as well as in combination with chemotherapy in patients with NSCLC, GC/GEJ adenocarcinoma, HNSCC or ESCC, with disease progression after prior therapy for advanced/metastatic disease.
To evaluate clinical activity, as assessed by ORR From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first. To evaluate the ORR of MCLA-129 monotherapy or in combination with an EGFR TKI or chemotherapy in molecularly defined populations of advanced/metastatic solid tumors.
- Secondary Outcome Measures
Name Time Method To evaluate preliminary antitumor activity in terms of BOR From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first. To evaluate preliminary antitumor activity of MCLA-129 monotherapy as well as in combination with an EGFR TKI or chemotherapy in terms of best overall response (BOR)
To evaluate preliminary antitumor activity in terms of DCR From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first. To evaluate preliminary antitumor activity of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Disease Control Rate (DCR).
To evaluate preliminary antitumor activity in terms of DoR From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first. To evaluate preliminary antitumor activity of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Duration of Response (DoR)
Proportion of patient with treatment discontinuations of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy. From first dose until study treatment discontinuation To evaluate progression-free survival (PFS) From first dose until RECIST progression or until 1 year after treatment, whichever occurs first. To evaluate progression-free survival (PFS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy From first dose until study treatment discontinuation To evaluate overall survival (OS) From first dose until RECIST progression or until 1 year after treatment, whichever occurs first. To evaluate overall survival (OS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.
AE, regardless of relationship to study treatment From first dose until study treatment discontinuation All safety endpoints From first dose until study treatment discontinuation including vital sign, lab, ECG, ECHO, 4 weeks CT scan, Eye exam
Trial Locations
- Locations (51)
Hôpital Bichat - Claude-Bernard
🇫🇷Paris, France
Hôpital Européen Georges Pompidou (HEGP)
🇫🇷Paris, France
CHU de Poitiers
🇫🇷Poitiers, France
Hôpital d'Instruction des Armées Bégin
🇫🇷Saint-Mandé, France
Krankenhaus Nordwest
🇩🇪Frankfurt am Main, Hesse, Germany
Sana Klinikum Offenbach GmbH
🇩🇪Offenbach am Main, Germany
Istituto Nazionale dei Tumori Regina Elena
🇮🇹Roma, Rome, Italy
Fundación Instituto Valenciano de Oncología (IVO)
🇪🇸Valencia, Spain
University of California, Irvine
🇺🇸Orange, California, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
Next Oncology Virginia
🇺🇸Fairfax, Virginia, United States
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
Antwerp University Hospital
🇧🇪Edegem, Belgium
Clinique de l'Europe
🇫🇷Amiens, France
CHU Hopitaux de Bordeaux - Hôpital Saint-André
🇫🇷Bordeaux, France
CHU de Lyon - Louis Pradel Hospital
🇫🇷Bron, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
Hôpital Albert Calmette
🇫🇷Lille, France
L'Institut Paoli - Calmettes
🇫🇷Marseille, France
CHU de Nantes - Hôpital Nord Laennec
🇫🇷Nantes, France
Marie Wislez
🇫🇷Paris, France
Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
ASST degli Spedali Civili di Brescia
🇮🇹Brescia, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
🇮🇹Salerno, Italy
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento
🇮🇹Verona, Italy
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital - Yonsei Cancer Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
National Cancer Centre of Singapore
🇸🇬Singapore, Singapore
Hospital HM Delfos
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
IOB Institute of Oncology - Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Clínica Universidad de Navarra -Madrid
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Centro Integral Oncológico Clara Campal
🇪🇸Madrid, Spain
Hospital Quirón Madrid
🇪🇸Madrid, Spain
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain