Dose Finding Study of GH35 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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Evaluate the safety and tolerability of GH35 in patients with KRAS mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in patients with KRAS mutant advanced solid tumors.

Official Title
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A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Primary Antitumor Activity of GH35 in Patients With Advanced Solid Tumors With KRAS Mutation

Conditions
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AdvAdvanced Solid Tumors, Kirsten Rat Sarcoma

Intervention / Treatment
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* Drug: GH35 Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects greater than or equal to 18 years old. Histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumor with KRAS mutation identified. Expected survival time ≥12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Must have at least one measureable lesion per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Have documented disease progression or intolerance after first-line treatment. Exclusion Criteria: Gastrointestinal (GI) tract disease causing the inability to take oral medication. Previous accept with KRAS G12C inhibitor. Uncontrollable general infection. Serious cardiovascular disease. Left ventricular ejection fraction (LVEF) <50 %. Known history of hypersensitivity to any of the excipients of GH35 tablets Pregnant or nursing (lactating) women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Dose Escalation.<br>Treatment with GH35 alone, conducted until disease progression, intolerance or end of study. | Drug: GH35 Tablet<br>* GH35 for oral administration at doses of Dose A, Dose B, Dose C, Dose D, Dose E and Dose F.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLT) | Number of participants with dose limiting toxicities (DLTs) | 24 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the safety of GH35 in subjects | Number of participants with treatment-emergent adverse events | 30 Months | 
| Evaluate the pharmacokinetics of GH35 | Blood plasma concentration | 1 Month | 
| Objective response rate (ORR) as assessed by RECIST 1.1 criteria |  | 30 Months | 
| Duration of response (DOR) as assessed by RECIST 1.1 criteria |  | 30 Months | 
| Progression-free survival (PFS) as assessed by RECIST 1.1 criteria |  | 30 Months | 
| Disease control rate (DCR) as assessed by RECIST 1.1 criteria |  | 30 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors, KRAS