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

Gastric Cancer Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04868877
• Other study ID #: MCLA-129-CL01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 28, 2021
• Est. completion date: April 2025

Study information

• Verified date: May 2023
• Source: Merus N.V.
• Contact: Merus Inquiries
• Phone: 617-401-4499
• Email: USenquiries[@]merus.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Gastric Cancer
• Head and Neck Squamous Cell Carcinoma
• Non-Small Cell Lung Cancer Metastatic
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• MCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
• Osimertinib
Approved, 3rd-generation EGFR-TKI

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Antwerp University Hospital	Edegem
France	Clinique de l'Europe	Amiens
France	CHU Hopitaux de Bordeaux - Hôpital Saint-André	Bordeaux
France	Institut Bergonié	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	Hôpital Bichat - Claude-Bernard	Paris
France	Hôpital Européen Georges Pompidou (HEGP)	Paris
France	Marie Wislez	Paris
France	CHU de Poitiers	Poitiers
France	CHU de Rennes - Hôpital Pontchaillou	Rennes
France	Hôpital d'Instruction des Armées Bégin	Saint-Mandé
Germany	Krankenhaus Nordwest	Frankfurt am Main	Hesse
Germany	Sana Klinikum Offenbach GmbH	Offenbach am Main
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	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	Milano
Italy	AOU L. Vanvitelli Universita degli Studi della Campania Luigi Vanvitelli	Napoli
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano
Italy	Istituto Nazionale dei Tumori Regina Elena	Roma	Rome
Italy	Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona	Salerno
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento	Verona
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Samsung Medical 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
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus Medical Center	Rotterdam
Singapore	National Cancer Centre of Singapore	Singapore
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital HM Delfos	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	IOB Institute of Oncology - Hospital Quironsalud Barcelona	Barcelona
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Clínica Universidad de Navarra -Madrid	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Quirón Madrid	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Fundación Instituto Valenciano de Oncología (IVO)	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United States	Next Oncology Virginia	Fairfax	Virginia
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of California, Irvine	Orange	California
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Merus N.V.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		First 28 days of treatment
Primary	To evaluate the ORR of MCLA-129 alone or in combination with Osimertinib in molecularly defined populations of advanced/metastatic solid tumors.		From first dose until 1 year after end of treatment or initiation of an alternative treatment, whichever occurs first.
Secondary	To evaluate preliminary antitumor activity in terms of best overall response (BOR)		Every 8 weeks until study ends, approximately 2 years
Secondary	To evaluate preliminary antitumor activity in terms of overall response rate (ORR)		Every 8 weeks until study ends, approximately 2 years
Secondary	To evaluate preliminary antitumor activity in terms of disease control rate (DCR)		Every 8 weeks until study ends, approximately 2 years
Secondary	To evaluate preliminary antitumor activity in terms of duration of response (DoR).		Every 8 weeks until study ends, approximately 2 years
Secondary	To evaluate progression-free survival (PFS)		Every 8 weeks until study ends, approximately 2 years
Secondary	To evaluate overall survival (OS).		Every 8 weeks until study ends, approximately 2 years
Secondary	Maximum plasma concentration [Cmax]		12 months
Secondary	Plasma concentration at 0 hours [C0h]		12 months
Secondary	Area under the concentration versus time curve from time zero to time t [AUC0-t]		12 months
Secondary	Area under the concentration versus time curve [AUC0-8]		12 months
Secondary	Time to reach maximum concentration [tmax]		12 months
Secondary	Half-life [t1/2]		12 months
Secondary	To assess changes in cytokines (TNFa) in serum blood following administration of MCLA-129		12 months
Secondary	To assess changes in cytokines (IFN?) in serum blood following administration of MCLA-129		12 months
Secondary	To assess changes in cytokines (IL-1ß) in serum blood following administration of MCLA-129		12 months
Secondary	To assess changes in cytokines (IL-2) in serum blood following administration of MCLA-129		12 months
Secondary	To assess changes in cytokines (IL-6) in serum blood following administration of MCLA-129		12 months
Secondary	Incidence of anti-drug antibodies in serum blood against MCLA-129		12 months
Secondary	Serum titers of anti-drug (MCLA-129) antibodies in serum blood		12 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0		12 months
Secondary	Proportion of patient with treatment discontinuations		12 months