This is a multicenter, open-label Phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of the anti-EGFR/c-Met bispecific antibody MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors.
Subjects should be aged 18-75 years (both inclusive), regardless of gender.
Subjects must have histologically or cytologically confirmed, locally advanced or metastatic solid tumors (including but not limited to non-small cell lung cancer, squamous cell carcinoma of the head and neck (primary site of oral cavity, oropharynx, hypopharynx, or larynx), gastric/gastroesophageal junction adenocarcinoma, etc.) that are not amenable to curative therapy.
Subjects must have MET amplification or MET overexpression as confirmed by the tests conducted by local or central laboratory.[MET amplification for Cohort 1 and Cohort 3 is defined as: MET copy number (CN) ≥ 5 by next-generation sequencing (NGS); or MET gene copy number (GCN) ≥ 5 or MET/CEP7 ≥ 2 by fluorescence in situ hybridization (FISH). MET amplification for Cohort 2 is defined as: MET copy number (CN) ≥ 3 by next-generation sequencing (NGS); or MET gene copy number (GCN) ≥ 3 or MET/CEP7 ≥ 2 by fluorescence in situ hybridization (FISH). MET overexpression is defined as 2+ or 3+ staining of ≥50% of tumor cells in tumor tissue samples by immunohistochemistry (IHC).]
For phase I study: subjects must meet the following conditions: with disease progression or intolerance to standard treatment after standard treatment, or evaluated by the investigator as ineligible for platinum-based chemotherapy (the standard treatment for the patient population enrolled in each cohort can refer to that for the phase II cohort study).
Subjects with non-small cell lung cancer who have been tested positive for ALK in the genetic tests conducted by the local or central laboratory.
Subjects have received any investigational drug or antitumor agent (for drugs with a long half-life, the time interval since the last dose should be no more than 4 weeks; for chemotherapy with delayed toxicity, such as nitrosoureas or mitomycin C, within the previous 6 weeks) within 14 days prior to the first dose of the study drug or within 5 half-lives of the drug (whichever is longer). Subjects have used any traditional Chinese medicine or Chinese herbal preparations with antitumor indications or definitive antitumor effects within 14 days prior to the first dose of the study drug.
Subjects who have undergone any major surgery or radiotherapy within 4 weeks prior to the first dose of the study drug (palliative local radiotherapy is allowed if it was administered at least 2 weeks prior to the first dose of the study drug).
For subjects with non-small cell lung cancer, prior receipt of more than two lines of systemic chemotherapy is required; for subjects with squamous cell carcinoma of the head and neck and gastric cancer/gastroesophageal junction adenocarcinoma, prior receipt of more than three lines of systemic anti-tumor treatment (excluding maintenance therapy) is required. For subjects who have received neoadjuvant/adjuvant therapy (chemotherapy or radio chemotherapy), if recurrence or metastasis occurs during treatment or within 6 months after discontinuation of treatment, it should be considered as first-line treatment.
Parallel
MCLA-129
DrugMCLA-129 is a bispecific antibody that targets both EGFR and c-Met, simultaneously blocking the signaling pathways of both EGFR and c-Met, thereby inhibiting tumor growth and survival.
Ensartinib
DrugEnsartinib acted as a c-MET inhibitor in this study.
Dose-Limiting Toxicity (DLT) in Phase I
To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of dose-limiting toxicity (DLT)
Maximum Tolerated Dose (MTD) in Phase I
To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of maximum tolerated dose (MTD)
Treatment-Emergent Adverse Events (TEAE) in Phase I
To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of treatment-emergent adverse event (TEAE)
Overall Response Rate (ORR) in Phase II
To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase II in terms of overall response rate (ORR)
Clinical benefit rate (CBR) in Phase I and II
To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase I and II in terms of clinical benefit rate (CBR)
Disease Control Rate (DCR) in Phase I and II
To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase I and II in terms of disease control rate (DCR)
Progression-Free Survival (PFS) in Phase I and II
To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase I and II in terms of progression-free survival (PFS)
Duration of Response (DOR) in Phase I and II
To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase I and II in terms of duration of response (DOR)
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