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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/1b Trial of MRTX849 in Combination With Palbociclib in Patients With Advanced Solid Tumors With KRAS G12C Mutation

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: MRTX849
* Drug: Palbociclib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination. | Drug: MRTX849<br>* KRAS G12C inhibitor<br>* Other names: adagrasib;Drug: Palbociclib<br>* CDK 4 and 6 inhibitor<br>* Other names: IBRANCE;|
| Experimental: Dose Expansion<br>Expansion cohorts may be implemented to ensure sufficient safety experience, pharmacokinetic data and early evidence of clinical activity of MRTX in combination with palbociclib. | Drug: MRTX849<br>* KRAS G12C inhibitor<br>* Other names: adagrasib;Drug: Palbociclib<br>* CDK 4 and 6 inhibitor<br>* Other names: IBRANCE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Number of participants with treatment emergent adverse events | 24 months | 
| Evaluate Pharmacokinetics of the combination regimen | Plasma concentration | 24 months | 
| Establish Maximum Tolerated Dose | Number of patients with dose limiting toxicity | 24 months | 
| Evaluate preliminary clinical activity of the combination regimen | Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) | 24 months |