Clinical trial NCT04868877: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer Metastatic
Gastric Cancer
Esophageal Squamous Cell Carcinoma
Head and Neck Squamous Cell Carcinoma
Colorectal Cancer
Keywords: MCLA-129
EGFR inhibitor
NSCLC
C-MET
GC/GEJ
Head and Neck Cancer
Lead sponsor: Merus N.V.
Sponsor class: INDUSTRY
First posted: 2021-05-03
Enrollment: 576
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Part One: 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 (as per protocol)

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 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

Primary outcomes:
measure: To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
timeFrame: First 28 days of treatment
measure: To evaluate clinical activity, as assessed by ORR
timeFrame: From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
Secondary outcomes:
measure: To evaluate preliminary antitumor activity in terms of BOR
timeFrame: From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
measure: To evaluate preliminary antitumor activity in terms of DCR
timeFrame: From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
measure: To evaluate preliminary antitumor activity in terms of DoR
timeFrame: From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
measure: To evaluate progression-free survival (PFS)
timeFrame: From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.
measure: To evaluate overall survival (OS)
timeFrame: From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.
measure: 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
timeFrame: From first dose until study treatment discontinuation
measure: Proportion of patient with treatment discontinuations of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.
timeFrame: From first dose until study treatment discontinuation
measure: AE, regardless of relationship to study treatment
timeFrame: From first dose until study treatment discontinuation
measure: All safety endpoints
timeFrame: From first dose until study treatment discontinuation
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: Next Oncology Virginia
state: Virginia
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Amiens
country: France
facility: Clinique de l'Europe
city: Bordeaux
country: France
facility: CHU Hopitaux de Bordeaux - Hôpital Saint-André
city: Bron
country: France
facility: CHU de Lyon - Louis Pradel Hospital
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Lille
country: France
facility: Hôpital Albert Calmette
city: Marseille
country: France
facility: L'Institut Paoli - Calmettes
city: Nantes
country: France
facility: CHU de Nantes - Hôpital Nord Laennec
city: Paris
country: France
facility: Marie Wislez
city: Paris
country: France
facility: Hôpital Bichat - Claude-Bernard
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP)
city: Poitiers
country: France
facility: CHU de Poitiers
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armées Bégin
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest
state: Hesse
city: Offenbach am Main
country: Germany
facility: Sana Klinikum Offenbach GmbH
city: Roma
country: Italy
facility: Istituto Nazionale dei Tumori Regina Elena
state: Rome
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Orbassano
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital - Yonsei Cancer Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Suwon, Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Singapore
country: Singapore
facility: National Cancer Centre of Singapore
city: Barcelona
country: Spain
facility: Hospital HM Delfos
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: IOB Institute of Oncology - Hospital Quironsalud Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra -Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Madrid
country: Spain
facility: Hospital Quirón Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología (IVO)
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
Study officials:
References: