Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

Study Overview
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Brief Summary
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This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed Description
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This study will evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and BI 1701963 is a SOS1 pan-KRAS inhibitor.

Official Title
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A Phase 1/1b Trial of MRTX849 in Combination With BI 1701963 in Patients With Advanced Solid Tumors With KRAS G12C Mutation

Conditions
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Advanced Cancer, Metastatic Cancer, Malignant Neoplasm of Colon, Malignant Neoplasm of Lung, Malignant Neoplastic Disease

Intervention / Treatment
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* Drug: MRTX849
* Drug: BI 1701963


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 (phase 1b must be either Non-Small Cell Lung Cancer or Colorectal Cancer) Unresectable or metastatic disease No available treatment with curative intent Adequate organ function 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 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 BI 1701963 to determine maximum tolerated dose in combination | Drug: MRTX849<br>* KRAS G12C inhibitor<br>* Other names: adagrasib;Drug: BI 1701963<br>* SOS1 Inhibitor<br>* Other names: SOS1 Inhibitor;|
| Experimental: Dose expansion<br>Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963 | Drug: MRTX849<br>* KRAS G12C inhibitor<br>* Other names: adagrasib;Drug: BI 1701963<br>* SOS1 Inhibitor<br>* Other names: SOS1 Inhibitor;|

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 related adverse events | 20 months | 
| Evaluate Pharmacokinetics of the combination regimen | Blood plasma concentration | 20 months | 
| Establish Maximum Tolerated Dose | Number of patients with dose limiting toxicity | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate preliminary clinical activity of the combination regimen | Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) | 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, CRC, KRAS G12C, SOS1 Inhibitor, Non Small Cell Lung Cancer, Colon Cancer, Advanced Solid Tumor, Metastatic Cancer, Pancreatic Cancer, adagrasib