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)

NCT05840510 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CA239-0011849-019
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Solid Tumor, Adult; NSCLC; Advanced Cancer; Metastatic Cancer; Malignant Neoplastic Disease

Keywords

KRAS; NSCLC; Adagrasib; KRAS G12C; mTOR; nab-sirolimus; Fyarro; ABI-009

Outcome Measures

Primary Outcomes (3)

• 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: 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)

  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)

  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 Outcomes (7)

• Area under the plasma concentration versus time curve (AUC)

  Up to 7 days

• Time to achieve maximal plasma concentration

  Up to 1 days

• Maximum observed plasma concentration

  Up to 1 days

• Terminal elimination half-life

  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.

  30 months

Study Arms (1)

Dose Escalation and Clinical Efficacy

EXPERIMENTAL

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; Drug: nab-Sirolimus

Interventions

Adagrasib DRUG

KRAS G12C inhibitor

Also known as: MRTX849, Krazati

Dose Escalation and Clinical Efficacy

nab-Sirolimus DRUG

mTOR inhibitor

Also known as: ABI -009, Fyarro

Dose Escalation and Clinical Efficacy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead
• Aadi Bioscience, Inc.: collaborator

Study Sites (3)

Local Institution - 019-104

Cleveland, Ohio, 44121, United States

Location

Local Institution - 019-101

Nashville, Tennessee, 37203, United States

Location

Local Institution - 019-102

Houston, Texas, 77030-4000, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

adagrasib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 3, 2023
• Study Start: August 7, 2023
• Primary Completion: December 27, 2024
• Study Completion: December 27, 2024
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)