GH21 Combined With D-1553 in KRAS G12C Mutant Advanced Solid Tumors

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation
• Intervention / Treatment: Drug: GH21; Drug: D-1553

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.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ZHENGBO SONG, DOCTORATE; Phone Number: +8613857153345; Email: zjccgcp_phase1@126.com
• Study Contact Backup: Name: Jieqi Tang, bachelor; Phone Number: +8613311557758; Email: tangjieqi@genhousebio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "GH21 + D-1553" Group; GH21 capsules combined with D-1553 tablets were administrated orally	Drug: GH21; GH21 Capsules, Oral Drug Specification: 3mg/capsule; 10mg/capsule; Drug: D-1553; D-1553 Film-coated Tablets, Oral Drug Sepcification: 200mg/tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicities Incidence Count Among Study	Incidence of dose limiting toxicities (DLTs) in the dose escalation phase.	2 years
Participants Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)Objective	All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs , etc	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor	2 years
response rate (ORR) based on RECIST 1.1 criteria	ORR is defined as the proportion of participants with complete response or partial response (CR+PR)	2 years
Duration of response (DOR) based on RECIST 1.1 criteria	DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.	2 years
Disease Control Rate (DCR) based on RECIST 1.1 criteria	DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD).	2 years
Progression-free survival (PFS) based on RECIST 1.1 criteria	PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first.	2 years
Plasma concentration (Cmax)	Peak Plasma concentration	2 years
Time to achieve Cmax (Tmax)	Time to achieve Cmax	2 years
Area under the plasma concentration-time curve (AUC)	Area under the plasma concentration-time curve	2 years

Collaborators and Investigators

• Sponsor: Suzhou Genhouse Bio Co., Ltd.
• Collaborators: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GH21C203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No