Colorectal Cancer, Esophageal Squamous Cell Carcinoma, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic
Conditions
Keywords
MCLA-129, EGFR inhibitor, NSCLC, C-MET, GC/GEJ, Head and Neck Cancer
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.
Interventions
DRUGMCLA-129
full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
DRUGOsimertinib
Approved, 3rd-generation EGFR-TKI
DRUGChemotherapy
administrated by IV infusion
Sponsors
Merus B.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 of MCLA-129 monotherapy as well as in combination with an EGFR TKI or chemotherapy in terms of best overall response (BOR) |
| 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 of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Disease Control Rate (DCR). |
| To evaluate preliminary antitumor activity in terms of DoR | From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first. | To evaluate preliminary antitumor activity of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Duration of Response (DoR) |
| To evaluate progression-free survival (PFS) | From first dose until RECIST progression or until 1 year after treatment, whichever occurs first. | To evaluate progression-free survival (PFS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy. |
| To evaluate overall survival (OS) | From first dose until RECIST progression or until 1 year after treatment, whichever occurs first. | To evaluate overall survival (OS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy. |
| 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 | — |
| 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 | — |
| AE, regardless of relationship to study treatment | From first dose until study treatment discontinuation | — |
| All safety endpoints | From first dose until study treatment discontinuation | including vital sign, lab, ECG, ECHO, 4 weeks CT scan, Eye exam |
Countries
Belgium, France, Germany, Italy, Netherlands, Singapore, South Korea, Spain, United States
Outcome results
None listed