Safety and Efficacy of Glumetinib Combined With Docetaxel for Injection (Albumin-bound) in Patients With Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma and Other Solid Tumors

Official title

A Multicenter, Open-label, Phase II Clinical Study to Evaluate the Safety and Efficacy of Glumetinib Combined With Docetaxel for Injection (Albumin-bound) in Patients With Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma and Other Solid Tumors With MET Overexpression and/or Amplification

Overview

The trial consists of Stage 1 (including dose escalation and dose expansion) and Stage 2 (proof-of-concept study). Among them, Stage 2 adopts a randomized, controlled, open-label, and multicenter design.

Interventions

• Drug Glumetinib Tablets
  glumetinib once daily once daily under fasting conditions in each 21-day treatment cycle.
• Drug Docetaxel for Injection (Albumin-bound)
  Docetaxel for Injection (Albumin-bound) by intravenous injection in each 21-day treatment cycle.

Primary outcome measures

• Dose escalation and cohort expansion phase: The occurrence and frequency of DLT (Dose-Limiting Toxicity) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: the occurrence and frequency of AE (Adverse Events) and SAE (Serious Adverse Events) (in accordance with NCI-CTCAE 5.0) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: Recommended Phase 2 Dose (RP2D) for the combination therapy. [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept phase: Objective Response Rate (ORR) evaluated by the Independent Review Committee (IRC) according to the RECIST 1.1 criteria. [Time frame: Up to approximately 24 months after the first patient is enrolled]

Secondary outcome measures (12)

• Dose escalation and cohort expansion phase: Evaluated by the Investigator according to the RECIST 1.1 criteria: Objective Response Rate (ORR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: Evaluated by the Investigator according to the RECIST 1.1 criteria: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: Evaluated by the Investigator according to the RECIST 1.1 criteria: Duration of Response (DoR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: Evaluated by the Investigator according to the RECIST 1.1 criteria: Progression-Free Survival (PFS) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Dose escalation and cohort expansion phase: Overall Survival (OS) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study：Evaluated by the Independent Review Committee (IRC) according to the RECIST 1.1 criteria: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study：Evaluated by the Independent Review Committee (IRC) according to the RECIST 1.1 criteria:Duration of Response (DoR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study：Evaluated by the Independent Review Committee (IRC) according to the RECIST 1.1 criteria: Progression-Free Survival (PFS) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study： Evaluated by the Investigator according to the RECIST 1.1 criteria: Objective Response Rate (ORR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study：Evaluated by the Investigator according to the RECIST 1.1 criteria: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study：Evaluated by the Investigator according to the RECIST 1.1 criteria: Duration of Response (DoR) [Time frame: Up to approximately 24 months after the first patient is enrolled]
• Proof-of-concept study： Evaluated by the Investigator according to the RECIST 1.1 criteria: Progression-Free Survival (PFS) [Time frame: Up to approximately 24 months after the first patient is enrolled]

Eligibility criteria

Inclusion criteria

• 1\. Patients who are able to understand and voluntarily sign the written ICF;
• 2\. Male or female patients aged ≥ 18 years (inclusive);
• 3\. Patients with advanced solid tumors diagnosed by pathology or cytology;
• 4\. Patients with a past medical history showing either negative or positive Her-2 expression can be enrolled. For those with unknown Her-2 expression, the Her-2 status needs to be determined before enrollment. For patients with positive Her-2 expression, their previous treatments should include anti-Her-2 drug therapy.
• 5\. Overexpression and/or amplification of MET in tumor tissue specimens/blood samples confirmed by the central laboratory.
• 6\. There are measurable lesions or non-measurable but evaluable lesions according to RECIST v1.1.
• 7\. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score is 0 or 1.
• 8\. The expected survival time is ≥ 3 months.
• 9\. The functions of major organs and bone marrow meet the criteria.

Exclusion criteria

• 1\. Patients with prior treatment with targeted MET drugs;
• 2\. Previous treatments included docetaxel;
• 3\. Patients with meningeal metastases, spinal cord compression, symptomatic or progressive brain metastases are not eligible for enrollment.
• 4\. Known hypersensitivity or intolerable conditions to any component of the drugs in the study protocol or their excipients.
• 5\. According to NCI-CTCAE 5.0, adverse events caused by previous anti-tumor treatment have not recovered to ≤ Grade 1 (excluding toxicities such as Grade 2 alopecia which are judged by the investigator to pose no safety risk).
• 6\. Any severe and/or uncontrolled co-existing diseases that may prevent the patient from participating in the study.
• 7\. Female patients who are lactating or pregnant; Women of childbearing potential with a positive blood pregnancy test result within 7 days before trial enrollment. Lactating women can participate in this study if they stop breastfeeding, but they must not resume breastfeeding during and after the completion of the study treatment.
• 8\. Any male or female patient of childbearing potential who refuses to use a highly effective contraceptive method throughout the trial period and within 6 months after the last administration.
• 9\. Those who are unwilling or unable to comply with the study procedures and requirements, or those who, in the judgment of the investigator, are not suitable for participating in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT06947291 · SYH2065-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗