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)

February 2, 2024 updated by: Mirati Therapeutics Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Interventional

Enrollment (Estimated)

79

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030-4000
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation and Clinical Efficacy
Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation
Drug: Adagrasib
KRAS G12C inhibitor
Other Names:
  • MRTX849
  • Krazati
Drug: nab-Sirolimus
mTOR inhibitor
Other Names:
  • Fyarro
  • ABI -009

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Safety and tolerability in the study population.
Time Frame: 30 months

Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:

  1. Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
  2. Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
  3. Number of patients modifying or discontinuing study treatment due to an AE
30 months
Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D)
Time Frame: 30 months
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the MTD/RP2D.
30 months
Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2)
Time Frame: 30 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration versus time curve (AUC)
Time Frame: Up to 7 days
AUC - nab-sirolimus and adagrasib
Up to 7 days
Time to achieve maximal plasma concentration
Time Frame: Up to 1 days
Tmax - nab-sirolimus and adagrasib
Up to 1 days
Maximum observed plasma concentration
Time Frame: Up to 1 days
Cmax - nab-sirolimus and adagrasib
Up to 1 days
Terminal elimination half-life
Time Frame: Up to 7 days
t1/2 - nab-sirolimus
Up to 7 days
Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population.
Time Frame: 30 months
  1. Overall survival is defined as time from date of randomization to date of death due to any cause.
  2. 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.
  3. 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
Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame: 30 months
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
Phase 2: Safety and tolerability in the study population.
Time Frame: 30 months

Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:

  1. Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
  2. Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
  3. Number of patients modifying or discontinuing study treatment due to an AE,
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mirati Therapeutics Inc.

Collaborators

Aadi Bioscience, Inc.

Investigators

  • Study Director: Richard Chao, MD, Mirati Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

April 12, 2023

First Submitted That Met QC Criteria

April 24, 2023

First Posted (Actual)

May 3, 2023

Study Record Updates

Last Update Posted (Estimated)

February 5, 2024

Last Update Submitted That Met QC Criteria

February 2, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 849-019

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

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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