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
MCLA-129: full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
Osimertinib: Approved, 3rd-generation EGFR-TKI
Chemotherapy: administrated by IV infusion
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)
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.
Trial sites (51)
Facility
City
Region
Status
University of California, Irvine
Orange
California
Sarah Cannon Research Institute
Nashville
Tennessee
START Mountain Region
West Valley City
Utah
Next Oncology Virginia
Fairfax
Virginia
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
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
Sana Klinikum Offenbach GmbH
Offenbach
Germany
Istituto Nazionale dei Tumori Regina Elena
Roma
Rome
Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
Bologna
Italy
ASST degli Spedali Civili di Brescia
Brescia
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan
Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
Orbassano
Italy
Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.