Back to resultsTrial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)
Primary Purpose
Advanced Cancer, Metastatic Cancer, Malignant Neoplasm of Lung
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Adagrasib
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Cancer focused on measuring KRAS G12C, Non-small cell lung cancer, Metastatic cancer, NSCLC
Eligibility Criteria
Key Inclusion Criteria: Are at least 18 years old (or old enough to legally make their own treatment decisions, according to local laws). Have advanced NSCLC or metastatic NSCLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation. Have had previous treatment with 1) chemotherapy that included a drug called cisplatin or a drug called carboplatin and 2) a type of drug called an immune checkpoint inhibitor. Have recovered from their prior treatment and blood tests are within a safe range. Key Exclusion Criteria: Have had previous treatment with a drug that targets KRAS G12C. Have cancer that can potentially be removed with surgery. Patients with brain lesions are not eligible if 1) any untreated brain lesions are > 2.0 cm in size 2) any brainstem lesions are present 3) ongoing steroid dosing >10 mg daily prednisone (or equivalent) and 4) poorly controlled (> 1/week) generalized or complex partial seizures or neurologic progression/instability due to brain lesions. Have certain medical conditions or need to take certain medications that, in the opinion of a trial doctor, could make it unsafe for them to participate or difficult to complete the trial assessments, or are pregnant.
Sites / Locations
- Providence Medical FoundationRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Adagrasib 600mg BID
Adagrasib 400mg BID
Arm Description
Adagrasib 600mg BID without regard to food
Adagrasib 400mg BID with food
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.
Secondary Outcome Measures
Evaluate Overall Survival (OS).
Overall survival is defined as time from date of randomization to date of death due to any cause.
Evaluate Progression Free Survival (PFS).
Progression-free survival is defined as time from date of randomization to date of first progression per RECIST 1.1 or death from any cause, whichever occurs first.
Evaluate Duration of Response (DOR).
Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD (per BICR review) or death due to any cause, whichever occurs first.
Safety and tolerability in the study population.
Safety characterized by number of participants with AEs, with abnormal laboratory test results and number of patients modifying or discontinuing study treatment due to an AE:
Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events.
Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment.
Number of patients modifying or discontinuing study treatment due to Adverse Event.
Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).
Sparse concentration data from this study will be pooled with other studies and analyzed using population PK methods to derive individual exposure parameters. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib.
Patient reported outcomes (PROs) will be used to assess symptomatic toxicity of adagrasib using the NCI Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. PRO items reflect the specific symptom 1) frequency, severity, interference with usual or daily activities, 2) amount, or 3) presence or absence. PRO-CTCAE responses are scored from 0 (low) to 4 (high), or 0/1 for absent/present, and scores for each attribute (frequency, severity and/or interference) are presented descriptively.
Patient -reported quality of life during adagrasib administration from first dose to End of Treatment visit.
Patient reported quality of life questionnaire will be used to assess five dimensions of patient health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using the 5-Level EQ-5D version (EQ-5D-5L) established by the EuroQol Group. This is presented descriptively, and patient responses correspond to a value of 1 (low) or 5 (high). Additionally, a one- page Visual Analog Scale (VAS) will be provided to patients so they may report their self-rated health from the best (100) and worst (0) health imaginable.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05853575
Brief Title
Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)
Official Title
A Randomized Study of Two Dosing Regimens of Adagrasib in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 5, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirati Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID versus 400 mg BID) in patients with NSCLC with KRAS G12C mutation.
Detailed Description
849-021 is a phase 2 study of adagrasib monotherapy in which patients are randomized between two dosing regimens. The study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID without regard to food versus 400 mg BID with food) in patients with NSCLC with KRAS G12C mutation and who have received prior treatment with a platinum-based regimen and immune checkpoint inhibitor therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Cancer, Metastatic Cancer, Malignant Neoplasm of Lung
Keywords
KRAS G12C, Non-small cell lung cancer, Metastatic cancer, NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Adagrasib 600mg BID
Arm Type
Experimental
Arm Description
Adagrasib 600mg BID without regard to food
Arm Title
Adagrasib 400mg BID
Arm Type
Experimental
Arm Description
Adagrasib 400mg BID with food
Intervention Type
Drug
Intervention Name(s)
Adagrasib
Other Intervention Name(s)
MRTX849, Krazati
Intervention Description
KRAS G12C inhibitor
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Description
ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
Evaluate Overall Survival (OS).
Description
Overall survival is defined as time from date of randomization to date of death due to any cause.
Time Frame
45 months
Title
Evaluate Progression Free Survival (PFS).
Description
Progression-free survival is defined as time from date of randomization to date of first progression per RECIST 1.1 or death from any cause, whichever occurs first.
Time Frame
30 months
Title
Evaluate Duration of Response (DOR).
Description
Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD (per BICR review) or death due to any cause, whichever occurs first.
Time Frame
30 months
Title
Safety and tolerability in the study population.
Description
Safety characterized by number of participants with AEs, with abnormal laboratory test results and number of patients modifying or discontinuing study treatment due to an AE:
Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events.
Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment.
Number of patients modifying or discontinuing study treatment due to Adverse Event.
Time Frame
30 months
Title
Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).
Description
Sparse concentration data from this study will be pooled with other studies and analyzed using population PK methods to derive individual exposure parameters. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame
Pre-dose and 4-6 hours post dose; up to 6 months.
Title
Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib.
Description
Patient reported outcomes (PROs) will be used to assess symptomatic toxicity of adagrasib using the NCI Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. PRO items reflect the specific symptom 1) frequency, severity, interference with usual or daily activities, 2) amount, or 3) presence or absence. PRO-CTCAE responses are scored from 0 (low) to 4 (high), or 0/1 for absent/present, and scores for each attribute (frequency, severity and/or interference) are presented descriptively.
Time Frame
30 months
Title
Patient -reported quality of life during adagrasib administration from first dose to End of Treatment visit.
Description
Patient reported quality of life questionnaire will be used to assess five dimensions of patient health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using the 5-Level EQ-5D version (EQ-5D-5L) established by the EuroQol Group. This is presented descriptively, and patient responses correspond to a value of 1 (low) or 5 (high). Additionally, a one- page Visual Analog Scale (VAS) will be provided to patients so they may report their self-rated health from the best (100) and worst (0) health imaginable.
Time Frame
30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Are at least 18 years old (or old enough to legally make their own treatment decisions, according to local laws).
Have advanced NSCLC or metastatic NSCLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation.
Have had previous treatment with 1) chemotherapy that included a drug called cisplatin or a drug called carboplatin and 2) a type of drug called an immune checkpoint inhibitor.
Have recovered from their prior treatment and blood tests are within a safe range.
Key Exclusion Criteria:
Have had previous treatment with a drug that targets KRAS G12C.
Have cancer that can potentially be removed with surgery.
Patients with brain lesions are not eligible if 1) any untreated brain lesions are > 2.0 cm in size 2) any brainstem lesions are present 3) ongoing steroid dosing >10 mg daily prednisone (or equivalent) and 4) poorly controlled (> 1/week) generalized or complex partial seizures or neurologic progression/instability due to brain lesions.
Have certain medical conditions or need to take certain medications that, in the opinion of a trial doctor, could make it unsafe for them to participate or difficult to complete the trial assessments, or are pregnant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mirati Therapeutics
Phone
1-844-893-5530
Email
miratistudylocator@emergingmd.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Meade, MD
Organizational Affiliation
Mirati Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Providence Medical Foundation
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ian Anderson, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)
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