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

Merus N.V.0 个研究点目标入组 600 人开始时间: 2022年9月6日最近更新: 2023年11月6日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Merus N.V.
入组人数: 600

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Signed informed consent before initiation of any study procedures.
•2. Age = 18 years at signature of informed consent.
•3. Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced unresected disease that is incurable:
•Dose Escalation Part - Patients 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. Patients must have:
•- Non-small cell lung cancer (NSCLC) harboring activating EGFR mutations including tyrosine kinase inhibitor (TKI) sensitizing mutations (e.g., 19del and L858R), and/or approved TKI-resistance mutations (e.g., acquired TKI-resistance mutations, i.e., T790M, C797S, L792, L798I, exon 20 insertion), or any activating c-MET mutation/amplification (e.g., high-level c-MET amplification [MET/CEP7 > 5 or cfDNA = 2 copies], or c-MET exon 14 skipping mutation).
•- Gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma harboring an EGFR amplification (EGFR/CEP7 =2 or cfDNA = 8 copies) or c-MET amplification (MET/CEP7 > 5 or cfDNA = 2 copies).
•- Head and neck squamous cell cancer (HNSCC) or esophageal squamous cell cancer (ESCC).
•Dose Expansion Part - Patients must have:
•Cohort A (closed to recruitment):
•- NSCLC harboring an EGFR exon 20 insertion, that has progressed after platinum doublets (a limited number of first line patients can be included). Previous treatment with bispecific EGFR/c-MET antibodies is allowed as there is no approved alternative available.
•Cohort B:
•- NSCLC harboring c-MET exon 14 skipping mutation =2L
•- Naive or pretreated to capmatinib and tepotinib
•Cohort C (closed to recruitment):
•- Selected solid tumors (GC/GEJ/pancreas/ESCC, GBM and PRCC) harboring an EGFR or c-MET alteration
•- NSCLC patients with other EGFR/c-MET alterations, not otherwise included in the other cohorts
•- Patients must have exhausted or be intolerant to all approved therapies with rationale for clinical benefit with MCLA-129
•Cohort C1 (closed to recruitment):
•- HNSCC refractory to approved treatment (regardless of driver mutations)
•Cohort D (closed to recruitment):
•- NSCLC 1L harboring EGFR sensitizing mutations (i.e. Del19, L858R)
•Cohort E (closed to recruitment):
•- NSCLC osimertinib resistant (participant must have progressed on or after a previous osimertinib monotherapy)
•*NOTE: Patient identification will be based on previous treatment history with TKIs, on local tests performed in CLIA-certified laboratories or on commercial diagnostics (e.g., FoundationOne). Genetic aberrations in EGFR or c-MET will be retrospectively confirmed by central testing using a validated assay in the expansion phase. For non-first line cohorts there is no limit to the number of prior treatment regimens.
•Cohort F:
•NSCLC 2L, osimertinib resistant, chemotherapy naïve population
•NSCLC 3L, osimertinib resistant, platinum resistant (participant must have progressed on or after a previous platinum chemotherapy) population
•4. Availability of tissue sample FFPE embedded after progression at the latest therapy (preferred in escalation, mandatory in expansion). Archival tumor tissue collected in the past may also be taken into consideration, but it is not preferred.
•5. Measurable disease as defined by RECIST version 1.1 by radiologic methods (patients with non-measurable but evaluable disease can be included i

排除标准

•1 Central nerv. system metastases that:
•-are untreated or symptomatic (patients with untreated, asymptomatic lesions can be included if in the inv. judgment considered clinically & radiologically stable)(exp. phase only)
•-require radiation or surgery(exp. phase only)
•-require continued steroid therapy (> 10 mg prednisone or equivalent) to control symptoms within 14 days of study entry
•2 Known leptomeningeal involvement(exp. phase only)
•3 Participation in another clinical study or treatment with any inv. drug within 4 weeks prior to study entry
•5 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 required. Note: For agents with long half-lives, enrollm. before the fifth half-life requires Sponsor approval. Cohort E patients can continue to receive osimertinib, as last treatm.
•6 Major surgery or radiotherapy within 3 weeks of the first dose. Patients who received prior radiotherapy to =25% of bone marrow at any time are not eligible. Pats. who received radiotherapy on lung at any time are not eligible
•7 Persistent Grade >1 clinically significant toxicities, in Investigator judgment, related to prior antineoplastic therapies (except alopecia); stable sensory neuropathy = Grade 2 NCI-CTCAE v5.0 and hypothyroidism = Grade 2 which is stable on hormone replacement are allowed
•8 History of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents
•9 History of clinically significant cardiovascular disease includ., but not limited to:
•Prolonged QT interval > 470 msec (for women) and > 450 msec (for men), obtained from 3 electrocardiograms, or clinically significant cardiac arrythmia, conduction or morphology of resting ECG (ie., complete left bundle branch block, third degree heart block and second degree heart block), 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. Pats. 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 in first-degree relatives or conc. medication known to prolong 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 defined as New York Heart Association class III-IV or hospitalization for CHF within 6 months of the first dose
•10 Past medical history of interstitial lung disease (ILD) or pneumonitis, or any evidence of clinically active ILD or pneumonitis
•11 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 & efficacy of the study drug(exp. phase only)
•13 Current serious illness or conditions including, but not limited to uncontrolled active infection, clinically significant p

研究者

发起方

Merus N.V.

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