Adagrasib in Combination With Palbociclib in Patients With Advanced Solid Tumors (KRYSTAL-16)

Phase 1

Completed

• Conditions: Advanced Solid Tumor
• Interventions: Drug: MRTX849; Drug: Palbociclib

• Registration Number: NCT05178888
• Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary

This study will evaluate the safety and clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid tumor malignancies with KRAS G12C mutation.

Detailed Description

This study will evaluate the pharmacokinetics and preliminary clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid tumor malignancies with KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and palbociclib is a small molecule inhibitor of CDK 4 and 6.

Study Timeline

• Study First Submitted: 2021-12-01
• Study First Submitted QC: 2022-01-04
• Study First Posted: 2022-01-05
• Study Start: 2022-01-20
• Primary Completion: 2023-06-15
• Study Completion: 2024-12-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-07
• Last Update Posted: 2025-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease.
• No available treatment with curative intent
• Adequate organ function

Exclusion Criteria

• History of significant toxicity on prior KRAS G12C or CDK4/6 inhibitor therapies
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter the absorption of study treatment or result in an inability to swallow
• Other active cancer
• Cardiac abnormalities

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	MRTX849	Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination.
Dose Escalation	Palbociclib	Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination.
Dose Expansion	Palbociclib	Expansion cohorts may be implemented to ensure sufficient safety experience, pharmacokinetic data and early evidence of clinical activity of MRTX in combination with palbociclib.
Dose Expansion	MRTX849	Expansion cohorts may be implemented to ensure sufficient safety experience, pharmacokinetic data and early evidence of clinical activity of MRTX in combination with palbociclib.

Primary Outcome Measures

Name	Time	Method
Characterize the number of patients with treatment emergent adverse events of the combination regimen in patients with advanced solid tumor malignancies with KRAS G12C mutation.	24 months	Number of participants with treatment emergent adverse events
Evaluate Pharmacokinetics of the combination regimen	24 months	Plasma concentration
Establish Maximum Tolerated Dose	24 months	Number of patients with dose limiting toxicity
Evaluate preliminary clinical activity of the combination regimen	24 months	Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Trial Locations

Locations (4)

Local Institution - 803; 🇺🇸 Nashville, Tennessee, United States

Local Institution - 804; 🇺🇸 Orlando, Florida, United States

Local Institution - 802; 🇺🇸 Houston, Texas, United States

Local Institution - 801; 🇺🇸 San Antonio, Texas, United States