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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Merus B.V.
- 入组人数
- 194
- 试验地点
- 51
- 主要终点
- To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Life expectancy ≥ 12 weeks, as per Investigator.
- •Adequate organ function (as per protocol)
排除标准
- •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
研究组 & 干预措施
Part 2 NSCLC Second-line or more harboring EGFR exon 20 Insertion
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
干预措施: MCLA-129 (Drug)
Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutation
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
干预措施: MCLA-129 (Drug)
Part 2 Selected solid tumors with or without an EGFR or cMet alteration
Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
干预措施: MCLA-129 (Drug)
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with 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.
干预措施: MCLA-129 (Drug)
Part 2 NSCLC First-line harboring EGFR sensitizing mutations
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.
干预措施: MCLA-129 (Drug)
Part 2 NSCLC First-line harboring EGFR sensitizing mutations
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.
干预措施: Osimertinib (Drug)
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with 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.
干预措施: Osimertinib (Drug)
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with 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.
干预措施: MCLA-129 (Drug)
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with 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.
干预措施: Chemotherapy (Drug)
Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with 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.
干预措施: MCLA-129 (Drug)
Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with 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.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
时间窗: 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
时间窗: 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.
次要结局
- 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 in terms of DCR(From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.)
- To evaluate preliminary antitumor activity in terms of DoR(From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.)
- 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.)
- 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.)
- AE, regardless of relationship to study treatment(From first dose until study treatment discontinuation)
- All safety endpoints(From first dose until study treatment discontinuation)