Clinical trial NCT06435455: GH21 Combined With D-1553 in KRAS G12C Mutant Advanced Solid Tumors
Official title: A Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of GH21 Capsule Combined With D-1553 Tablets in Patients With Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation
Lead sponsor: Suzhou Genhouse Bio Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Zhejiang Cancer Hospital
First posted: 2024-05-30
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This s a multi-center, open-label phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of GH21 combined with D-1553 in patients with advanced or metastatic solid tumors harboring KRAS G12C mutation.

Detailed description: This study includes 2 parts: dose escalation(Phase Ib) and dose expansion (Phase II). The objective of the dose escalation part is to evaluate the safety, tolerability and pharmacokinetics of GH21 in combination with D-1553 in patients with advanced solid tumors harboring KRAS G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion part, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS G12C mutation.

Eligibility criteria: Inclusion Criteria:

* The patient or his legal representative is able to understand and voluntarily sign a written informed consent (before commencing this study and any research procedure);
* Age ≥18 years old, male or female;
* KRAS G12C mutant advanced solid tumor;
* ECOG Performance Status of 0 or 1
* At least one measurable lesion as defined by RECIST 1.1

Exclusion Criteria:

* acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, cerebrovascular accident, or transient ischemic attack within 6 months before first administration; Grade III-IV heart failure based on the New York Heart Association Cardiac Function Scale at screening; During screening, echocardiography (ECHO) showed left ventricular ejection fraction (LVEF) ≤50%;
* Patients who have a history of severe allergy, or have a history of allergy to the experimental drug/any excipient/combination drug, or have a history of allergy to multiple drugs;
* There is an active infection (≥ grade 2) requiring anti-infective treatment or an unexplained fever exceeding 38 ° C within 28 days before the first dose;
* Any toxicity from previous antitumor therapy prior to initial administration has not returned to CTCAE 5.0 rating ≤ Class 1 (unless hair loss, grade 2 peripheral neuropathy, and/or other grade ≤2 adverse events that do not pose a safety risk);
* Pregnant and lactating women;
* The investigator considers that there are any clinical or laboratory abnormalities or other reasons to be unsuitable for participating in this clinical study.

Primary outcomes:
measure: Dose-limiting Toxicities Incidence Count Among Study
timeFrame: 2 years
measure: Participants Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)Objective
timeFrame: 2 years
Secondary outcomes:
measure: response rate (ORR) based on RECIST 1.1 criteria
timeFrame: 2 years
measure: Duration of response (DOR) based on RECIST 1.1 criteria
timeFrame: 2 years
measure: Disease Control Rate (DCR) based on RECIST 1.1 criteria
timeFrame: 2 years
measure: Progression-free survival (PFS) based on RECIST 1.1 criteria
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Plasma concentration (Cmax)
timeFrame: 2 years
measure: Time to achieve Cmax (Tmax)
timeFrame: 2 years
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
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