Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation
Conditions
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.
Interventions
Sponsors
Zhejiang Cancer Hospital
Suzhou Genhouse Bio Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicities Incidence Count Among Study | 2 years | Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. |
| Participants Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)Objective | 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) based on RECIST 1.1 criteria | 2 years | DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). |
| Progression-free survival (PFS) based on RECIST 1.1 criteria | 2 years | 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. |
| Overall survival (OS) | 2 years | 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 |
| response rate (ORR) based on RECIST 1.1 criteria | 2 years | ORR is defined as the proportion of participants with complete response or partial response (CR+PR) |
| Time to achieve Cmax (Tmax) | 2 years | Time to achieve Cmax |
| Area under the plasma concentration-time curve (AUC) | 2 years | Area under the plasma concentration-time curve |
| Plasma concentration (Cmax) | 2 years | Peak Plasma concentration |
| Duration of response (DOR) based on RECIST 1.1 criteria | 2 years | 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. |
Contacts
Primary ContactJieqi Tang, bachelor
Backup ContactZhengbo Song, Doctorate
Outcome results
None listed