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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05840510
Other study ID # CA239-0011
Secondary ID CA239-0011849-01
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date August 7, 2023
Est. completion date June 30, 2026

Study information

Verified date June 2024
Source Mirati Therapeutics Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation.


Description:

This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors harboring a KRAS G12C mutation. The Phase 1 portion will enroll advanced solid tumors to establish the maximum tolerated dose (MTD) and/or to identify recommended Phase 2 combinatorial doses. The Phase 2 portion will enroll patients with NSCLC to further evaluate the safety/tolerability and clinical activity. Adagrasib is an orally available small molecule inhibitor of KRAS G12C. nab-Sirolimus is a nanoparticle albumin-bound (nab) form of sirolimus, and sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin).


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 79
Est. completion date June 30, 2026
Est. primary completion date December 31, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologically confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function - Measurable disease per RECIST 1.1. Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - History of interstitial lung disease or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease or pneumonitis - Cardiac abnormalities

Study Design


Intervention

Drug:
Adagrasib
KRAS G12C inhibitor
nab-Sirolimus
mTOR inhibitor

Locations

Country Name City State
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States University of Texas MD Anderson Cancer Center Houston Texas
United States SCRI Oncology Partners Nashville Tennessee

Sponsors (2)

Lead Sponsor Collaborator
Mirati Therapeutics Inc. Aadi Bioscience, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 1: Safety and tolerability in the study population. Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:
Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
Number of patients modifying or discontinuing study treatment due to an AE
30 months
Primary Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) Evaluate safety and assess number of patients with dose-limiting toxicity to determine the MTD/RP2D. 30 months
Primary Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2) ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment. 30 months
Secondary Area under the plasma concentration versus time curve (AUC) AUC - nab-sirolimus and adagrasib Up to 7 days
Secondary Time to achieve maximal plasma concentration Tmax - nab-sirolimus and adagrasib Up to 1 days
Secondary Maximum observed plasma concentration Cmax - nab-sirolimus and adagrasib Up to 1 days
Secondary Terminal elimination half-life t1/2 - nab-sirolimus Up to 7 days
Secondary Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population. Overall survival is defined as time from date of randomization to date of death due to any cause.
Progression-free survival is defined as the time from randomization to the date of Progressive Disease (PD) or death due to any cause,whichever occurs first.
Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD or death due to any cause, whichever occurs first.
30 months
Secondary Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with advanced solid tumors and NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment. 30 months
Secondary Phase 2: Safety and tolerability in the study population. Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:
Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
Number of patients modifying or discontinuing study treatment due to an AE,
30 months
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