Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)

• ClinicalTrials.gov Identifier: NCT04793958
• Recruitment Status: Active, not recruiting
• First Posted: March 11, 2021
• Last Update Posted: March 15, 2024
• Sponsor: Mirati Therapeutics Inc.
• Information provided by (Responsible Party): Mirati Therapeutics Inc.

Tracking Information

• First Submitted Date: March 2, 2021
• First Posted Date: March 11, 2021
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: February 28, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2021)

• Overall Survival (OS) [ Time Frame: 30 months ]
  Defined as time from date of randomization to date of death due to any cause.
• Progression-free Survival (PFS) [ Time Frame: 30 months ]
  Defined as time from randomization until disease progression or death from any cause, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 8, 2021)

• Adverse Events [ Time Frame: 30 months ]
  Defined as number of patients with treatment emergent AEs.
• Objective Response Rate (ORR) [ Time Frame: 30 months ]
  Defined as the percent of patients documented to have a confirmed CR or PR.
• Duration of Response (DOR) [ Time Frame: 30 months ]
  Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.
• Patient Reported Outcomes (PROs) [ Time Frame: 30 months ]
  To be assessed by European Quality of Life Questionnaire for Cancer Patients (QLQ-C30).
• Quality of Life Assessment [ Time Frame: 30 months ]
  To be assessed by European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)
• Official Title: A Randomized Phase 3 Study of MRTX849 in Combination With Cetuximab Versus Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation With Disease Progression On or After Standard First-Line Therapy
• Brief Summary: Study 849-010 is an open-label, randomized Phase 3 clinical trial comparing the efficacy of MRTX849 administered in combination with cetuximab versus chemotherapy in the second-line treatment setting in patients with CRC with KRAS G12C mutation.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Colorectal Cancer
• Metastatic Colorectal Cancer

Intervention

• Drug: MRTX849
  28 Day Cycle
• Biological: Cetuximab
  28 Day Cycle
  Other Name: Erbitux
• Drug: mFOLFOX6 Regimen
  • Fluorouracil
  • Oxaliplatin
  • Folinic acid
• Drug: FOLFIRI Regimen
  • Fluorouracil
  • Irinotecan
  • Folinic acid

Study Arms

• Experimental: MRTX849 + Cetuximab
  Interventions:

  • Drug: MRTX849
  • Biological: Cetuximab
• Active Comparator: mFOLFOX6 or FOLFIRI
  Interventions:

  • Drug: mFOLFOX6 Regimen
  • Drug: FOLFIRI Regimen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 4, 2024): 461
• Original Estimated Enrollment (submitted: March 8, 2021): 420
• Estimated Study Completion Date: February 28, 2026
• Estimated Primary Completion Date: February 28, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue.
• Prior receipt of 1st line treatment in advanced CRC with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan, and radiographically documented progression of disease on or after treatment.

Exclusion Criteria:

• Prior treatment with a therapy targeting KRAS G12C mutation (e.g., AMG 510).
• Prior treatment with an anti-EGFR antibody (e.g., cetuximab or panitumumab).
• Active brain metastasis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Ireland, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT04793958
• Other Study ID Numbers: 849-010; KRYSTAL-10 ( Other Identifier: Mirati Therapeutics )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Mirati Therapeutics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Mirati Therapeutics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Hirak Der-Torossian, MD; Mirati Therapeutics

• PRS Account: Mirati Therapeutics Inc.
• Verification Date: March 2024