Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Dose escalation Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination |
Drug: MRTX849
KRAS G12C inhibitor
Other Names:
Drug: BI 1701963
SOS1 Inhibitor
Other Names:
|
Experimental: Dose expansion 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
KRAS G12C inhibitor
Other Names:
Drug: BI 1701963
SOS1 Inhibitor
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 [20 months]
Number of participants with treatment related adverse events
- Evaluate Pharmacokinetics of the combination regimen [20 months]
Blood plasma concentration
- Establish Maximum Tolerated Dose [12 months]
Number of patients with dose limiting toxicity
Secondary Outcome Measures
- Evaluate preliminary clinical activity of the combination regimen [20 months]
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
2 | The Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
3 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
4 | Next Oncology | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Mirati Therapeutics Inc.
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 849-014