Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19)

Metastatic Cancer Clinical Trial

Official title:

A Phase 1/2 Trial of Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05840510
• Other study ID #: 849-019
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 7, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: May 2024
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• 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

Related Conditions & MeSH terms

• Advanced Cancer
• Malignant Neoplastic Disease
• Metastatic Cancer
• Neoplasms
• NSCLC
• Solid Tumor, Adult

Intervention

Drug:
• Adagrasib
KRAS G12C inhibitor
• nab-Sirolimus
mTOR inhibitor

Locations

Country	Name	City	State
United States	Research Site	Cleveland	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	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