Clinical trial NCT04330664: Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)
Official title: A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Metastatic Cancer
Malignant Neoplastic Disease
Keywords: KRAS G12C
Non-small cell lung cancer
Colorectal Cancer
Colon Cancer
Metastatic Cancer
Pancreatic Cancer
NSCLC
SHP2
Advanced Solid Tumors
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2020-04-01
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed description: This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.

This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 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

Primary outcomes:
measure: Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
timeFrame: 20 months
measure: Evaluate the pharmacokinetics of MRTX849 and TNO155
timeFrame: 20 months
Secondary outcomes:
measure: Establish maximum tolerated dose
timeFrame: 12 months
measure: Evaluate clinical activity of MRTX849
timeFrame: 20 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 002-805
state: California
city: Orange
country: United States
facility: Local Institution - 002-803
state: California
city: Chicago
country: United States
facility: Local Institution - 002-828
state: Illinois
city: Wichita
country: United States
facility: Local Institution - 002-942
state: Kansas
city: Boston
country: United States
facility: Local Institution - 002-804
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 002-808
state: Massachusetts
city: Novi
country: United States
facility: Local Institution - 002-811
state: Michigan
city: Creve Coeur
country: United States
facility: Local Institution - 002-809 B
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 002-809 A
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 002-809 C
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 002-809
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 002-809 E
state: Missouri
city: Saint Peters
country: United States
facility: Local Institution - 002-809 D
state: Missouri
city: New York
country: United States
facility: Local Institution - 002-813
state: New York
city: New York
country: United States
facility: Local Institution - 002-806
state: New York
city: San Antonio
country: United States
facility: Local Institution - 002-801
state: Texas
city: Milwaukee
country: United States
facility: Local Institution - 002-810
state: Wisconsin
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: