Trial Outcomes & Findings for Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation (NCT NCT04685135)

Last Updated: 2025-01-22

Results Overview

Progression-free survival (PFS) is defined as the time from randomization to the date of progression or death due to any cause, whichever occurs first. 95% CI was obtained using Brookmeyer and Crowley method. Participants who are not observed to have progressed or died are censored at the date of last evaluable tumor assessment. Disease progression assessed as per RECISIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

453 participants

Primary outcome timeframe

From randomization to the date of progression or death due to any cause, whichever occurs first (up to approximately 143 weeks)

Results posted on

2025-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Adagrasib Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.
Overall Study STARTED	301	152
Overall Study Safety Population	298	140
Overall Study Cross Over	0	44
Overall Study COMPLETED	163	83
Overall Study NOT COMPLETED	138	69

Reasons for withdrawal

Reasons for withdrawal
Measure	Adagrasib Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.
Overall Study Death	126	53
Overall Study Withdrawal by Subject	12	16

Baseline Characteristics

Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Total n=453 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 8.66 • n=5 Participants	63.9 years STANDARD_DEVIATION 7.81 • n=7 Participants	63.7 years STANDARD_DEVIATION 8.38 • n=5 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	42 Participants n=7 Participants	150 Participants n=5 Participants
Sex: Female, Male Male	193 Participants n=5 Participants	110 Participants n=7 Participants	303 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=5 Participants	111 Participants n=7 Participants	310 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	94 Participants n=5 Participants	35 Participants n=7 Participants	129 Participants n=5 Participants
Race/Ethnicity, Customized White	135 Participants n=5 Participants	81 Participants n=7 Participants	216 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	72 Participants n=5 Participants	37 Participants n=7 Participants	109 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	81 Participants n=5 Participants	30 Participants n=7 Participants	111 Participants n=5 Participants
Race/Ethnicity, Customized Missing	11 Participants n=5 Participants	3 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to the date of progression or death due to any cause, whichever occurs first (up to approximately 143 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Progression-Free Survival (PFS) as Per Blinded Independent Central Review	5.49 months Interval 4.53 to 6.67	3.84 months Interval 2.73 to 4.73	—	—	—

SECONDARY outcome

Timeframe: From randomization till death due to any cause (up to approximately 143 weeks)

Overall survival is defined as the time from randomization to the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization till death or till disease progression or initiation of follow-up anti-cancer therapy or withdrawal of consent prior to minimum efficacy follow-up (up to 143 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

Objective Response Rate (ORR) is defined as the percent of participants documented to have a confirmed complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. All target lesions must be assessed. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Objective Response Rate (ORR) as Per Blinded Independent Central Review	31.9 percentage of participants Interval 26.7 to 37.5	9.2 percentage of participants Interval 5.1 to 15.0	—	—	—

SECONDARY outcome

Timeframe: First documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause (Up to approximately 22 months)

Population: Intent-To-Treat Population with Confirmed CR or PR. Intent-To-Treat Population includes all participants who are randomized into this study.

Duration of Response (DOR) in months is defined as the time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. All target lesions must be assessed. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.

Outcome measures

Outcome measures
Measure	Adagrasib n=96 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=14 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Duration of Response (DOR) as Per Blinded Independent Central Review	8.31 months Interval 6.05 to 10.35	5.36 months Interval 2.86 to 8.54	—	—	—

SECONDARY outcome

Timeframe: Up to 49 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)

Population: Safety Population included all the participants who received at least one dose of the study drug. Docetaxel arm do not include adverse events after initiation of crossover Adagrasib treatment.

Treatment Emergent Adverse Events (TEAEs) are those that first occur or increase in severity on or after the first dose and not more than 28 days after the last dose, and prior to the initiation of subsequent systemic anti-cancer therapy. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Adagrasib n=298 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=140 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib n=44 Participants Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any TEAE	298 Participants	138 Participants	44 Participants	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any Treatment-Related TEAE	280 Participants	121 Participants	41 Participants	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any Treatment-Emergent SAE	149 Participants	50 Participants	20 Participants	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any Treatment-Related Treatment-Emergent SAE	62 Participants	23 Participants	7 Participants	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any TEAE Leading to Discontinuation of Treatment	40 Participants	25 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)

Blood samples were collected to assess hematology parameters. Adverse events are graded on a scale from 0 to 4 based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with Grade 0 being normal Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization.

Outcome measures

Outcome measures
Measure	Adagrasib n=298 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=140 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib n=44 Participants Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Grade 0	50 Participants	16 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Grade 2	74 Participants	34 Participants	7 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Grade 3	16 Participants	8 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Missing	3 Participants	8 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Grade 0	61 Participants	33 Participants	9 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Grade 1	66 Participants	20 Participants	7 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Grade 4	8 Participants	3 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Missing	40 Participants	28 Participants	9 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Grade 2	8 Participants	7 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Grade 3	4 Participants	10 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Grade 4	8 Participants	21 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Grade 0	208 Participants	113 Participants	35 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Grade 1	74 Participants	13 Participants	6 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Grade 2	8 Participants	3 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Grade 3	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Missing	4 Participants	11 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Grade 2	16 Participants	15 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Grade 3	7 Participants	24 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Missing	4 Participants	11 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Anemia Grade 1	155 Participants	74 Participants	26 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Grade 2	71 Participants	33 Participants	10 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Lymphocytes count decreased Grade 3	52 Participants	23 Participants	9 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Grade 0	227 Participants	61 Participants	32 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Grade 1	10 Participants	13 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Neutrophils count decreased Missing	41 Participants	28 Participants	9 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters Platelets count decreased Grade 4	3 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Grade 0	235 Participants	72 Participants	36 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Grade 1	36 Participants	14 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters White blood cell decreased Grade 4	0 Participants	4 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)

Blood samples were collected to assess chemistry parameters. Adverse events are graded on a scale from 0 to 4 based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with Grade 0 being normal Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization.

Outcome measures

Outcome measures
Measure	Adagrasib n=298 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=140 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib n=44 Participants Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Grade 2	1 Participants	0 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Grade 3	13 Participants	0 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Missing	18 Participants	16 Participants	6 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Grade 0	265 Participants	122 Participants	37 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Grade 1	19 Participants	4 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Grade 3	1 Participants	1 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Missing	13 Participants	13 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Grade 4	2 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Missing	134 Participants	72 Participants	23 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Grade 0	177 Participants	109 Participants	28 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Grade 1	63 Participants	9 Participants	7 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Lipase Increased Grade 2	27 Participants	6 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Grade 1	107 Participants	12 Participants	11 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Grade 3	34 Participants	0 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Missing	11 Participants	10 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Grade 2	58 Participants	22 Participants	7 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Grade 1	24 Participants	19 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Grade 2	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Grade 4	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Grade 2	11 Participants	2 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Grade 4	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Grade 2	16 Participants	3 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Grade 0	103 Participants	115 Participants	25 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Missing	12 Participants	11 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Grade 1	24 Participants	2 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Grade 3	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Grade 4	2 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Missing	11 Participants	12 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Grade 2	126 Participants	11 Participants	15 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Grade 4	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Missing	11 Participants	10 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Grade 1	15 Participants	4 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypermagnesemia Grade 2	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Grade 0	163 Participants	66 Participants	22 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Grade 2	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Grade 4	3 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Grade 2	20 Participants	6 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Grade 3	5 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Grade 4	1 Participants	1 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Missing	12 Participants	11 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Grade 1	14 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Grade 2	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Grade 0	135 Participants	95 Participants	18 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Grade 1	126 Participants	32 Participants	19 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Grade 2	17 Participants	3 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Grade 3	7 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Missing	11 Participants	10 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Grade 0	251 Participants	125 Participants	37 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Bilirubin increased Grade 2	9 Participants	1 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Grade 3	6 Participants	3 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Fasted Hypoglycemia Grade 0	146 Participants	64 Participants	18 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Grade 0	99 Participants	99 Participants	14 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Creatinine increased Grade 1	55 Participants	17 Participants	9 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Grade 0	118 Participants	118 Participants	23 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Grade 2	23 Participants	0 Participants	4 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alanine Aminotransferase increased Grade 4	5 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Grade 0	118 Participants	55 Participants	19 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Grade 1	109 Participants	51 Participants	13 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Grade 3	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypoalbuminemia Missing	12 Participants	12 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Grade 0	260 Participants	108 Participants	35 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypercalcemia Missing	12 Participants	13 Participants	6 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Grade 0	230 Participants	111 Participants	25 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Grade 1	45 Participants	14 Participants	11 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypocalcemia Missing	12 Participants	13 Participants	6 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Grade 0	165 Participants	109 Participants	24 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Grade 1	82 Participants	19 Participants	14 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Grade 2	31 Participants	2 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Grade 3	8 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Alkaline Phosphatase increased Missing	11 Participants	10 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Grade 0	181 Participants	107 Participants	31 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Grade 1	65 Participants	11 Participants	7 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Grade 3	6 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Amylase increased Missing	30 Participants	19 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Grade 1	133 Participants	14 Participants	13 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Grade 2	27 Participants	0 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Grade 3	20 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Aspartate Aminotransferase increased Grade 4	3 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Grade 0	213 Participants	99 Participants	29 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Grade 1	67 Participants	25 Participants	10 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Grade 2	5 Participants	3 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypomagnesemia Missing	13 Participants	13 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Grade 1	9 Participants	8 Participants	3 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Non-Fasted Hypoglycemia Missing	122 Participants	66 Participants	19 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Grade 0	206 Participants	107 Participants	28 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperkalemia Grade 1	54 Participants	15 Participants	8 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Grade 0	237 Participants	114 Participants	36 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Grade 1	43 Participants	11 Participants	2 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Grade 2	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Grade 3	6 Participants	3 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Grade 4	0 Participants	1 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypokalemia Missing	12 Participants	11 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Grade 0	272 Participants	130 Participants	39 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Grade 3	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hypernatremia Missing	11 Participants	10 Participants	5 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyponatremia Grade 4	2 Participants	0 Participants	1 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Grade 0	185 Participants	103 Participants	22 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Grade 1	98 Participants	22 Participants	17 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Grade 2	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Grade 3	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Grade 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters Hyperuricemia Missing	15 Participants	15 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (Pre-Dose and Peak), Cycle 2 (Pre-Dose and Peak), Cycle 3 (Pre-Dose), Cycle 5 (Pre-Dose), Cycle 7 (Pre-Dose) (Each cycle is of 21 days)

Population: The PK evaluable population is defined as patients who received at least one dose of active study drug and had at least one blood sample collected to assess PK concentrations

Blood samples were collected for assessment of plasma concentration of Adagrasib. Data for participants for which the dose was reduced after receiving starting dose of 600 mg BID, based on physician decision is presented in separate arms.

Outcome measures

Outcome measures
Measure	Adagrasib n=1 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=2 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib n=48 Participants Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD n=15 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID n=295 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Plasma Concentration of Adagrasib Cycle 1 Day 1 Pre-Dose	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	—	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA
Plasma Concentration of Adagrasib Cycle 2 Day 1 Pre-Dose	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	—	1579.040 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 54.432	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	2097.813 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 67.912
Plasma Concentration of Adagrasib Cycle 3 Day 1 Pre-Dose	—	—	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	1865.408 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 42.930
Plasma Concentration of Adagrasib Cycle 5 Day 1 Pre-Dose	—	—	1114.046 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 39.300	917.541 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 73.596	1459.470 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 39.094
Plasma Concentration of Adagrasib Cycle 1 Day 1 Peak	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	—	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	556.963 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 63.550	518.944 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 86.625
Plasma Concentration of Adagrasib Cycle 2 Day 1 Peak	—	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	2011.347 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 39.333	2331.298 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 59.515	2117.333 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 62.744
Plasma Concentration of Adagrasib Cycle 7 Day 1 Pre-Dose	—	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Concentrations that are below the limit of quantification (BLQ) are treated as NA	1062.114 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 33.842	863.539 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 42.917	1548.018 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 41.166

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire assesses the following 6 symptoms items (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and 3 summary global items (symptom distress, activity level, overall quality of life) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The LCSS average total score is sum of items 1 to 9 divided by the total number of items ((sum of items 1 to 9)/9) ranging from 0 to 100 where high score represent worst outcome. Least Square Mean and Confidence Interval are from a repeated measures model on the response variable change from baseline in LCSS average total score.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Total Score	-4.0 Score on a sclae Interval -7.9 to -0.2	3.9 Score on a sclae Interval -0.2 to 8.0	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire for average symptom burden index score assesses the following six items (Appetite loss, fatigue, cough, shortness of breath, blood in sputum, pain) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The average symptom burden score is average of all the 6 items ranging from 0 to 100 where high score represent worst outcome. Least square mean and CI are from a repeated measures model on the response variable change from baseline in average symptom burden index score.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index Score	-5.8 Score on a sclae Interval -9.0 to -2.5	3.2 Score on a sclae Interval -0.4 to 6.7	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire for average 3-item global index score assesses the following 3 items (Distress/severity of symptoms from lung cancer, impact on normal activities, quality of life) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The 3 item global index score is average of all the 3 items ranging from 0 to 100 where high score represent worst outcome. LS mean and CI are from a repeated measures model on the response variable change from baseline in 3-item global index score.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Change From Baseline in Lung Cancer Symptom Scale (LCSS) 3-Item Global Index Score	-3.0 Score on a sclae Interval -20.3 to 14.3	15.9 Score on a sclae Interval -2.6 to 34.3	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study. LS mean and CI are from a repeated measures model on the response variable change from baseline in visual analogue scale.

The Visual Analogue Score (VAS) is a component of the EQ-5D-5L and assesses the patient's self-rated health using a vertical visual analogue scale where numbered 0 (the worst health you can image) to 100 (the best health you can imageine). The smallest change considered clinically meaningful, is defined as a score difference of 7 points.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Visual Analogue Scale Score	0.1 Score on a scale Interval -4.4 to 4.5	-3.7 Score on a scale Interval -8.5 to 1.1	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Population: Intent-To-Treat Population includes all participants who are randomized into this study.

The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.594 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points. Least square mean and CI are from a repeated measures model on the response variable change from baseline in health utility index.

Outcome measures

Outcome measures
Measure	Adagrasib n=301 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with Adagrasib tablet or capsule orally at a starting dose of 600 mg twice a day (BID).	Docetaxel n=152 Participants Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered in 3-week cycle with intravenous infusion of Docetaxel at 75 mg/m\^2 over 1 hour or according to institutional practices.	Crossover Adagrasib Eligible participants receiving Docetaxel earlier in the study switched to Adagrasib based on physician decision. Participants were administered with Adagrasib orally at a starting dose of 600 mg twice a day (BID).	Adagrasib 600 mg QD Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg QD Adagrasib orally.	Adagrasib 600 mg BID Participants with Non Small Cell Lung Cancer (NSCLC) with KRAS G12C mutation and who have received prior therapy with a platinum-based regimen and an immune checkpoint inhibitor were administered with study treatment in 3-week cycle and were administered 600 mg BID Adagrasib orally.
Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Health Utility Index Score	-0.0350 Score on a scale Interval -0.0977 to 0.0277	-0.0914 Score on a scale Interval -0.1572 to -0.0256	—	—	—

Adverse Events

Adagrasib

Serious events: 149 serious events

Other events: 292 other events

Deaths: 126 deaths

Docetaxel

Serious events: 50 serious events

Other events: 129 other events

Deaths: 53 deaths

Crossover Adagrasib

Serious events: 20 serious events

Other events: 43 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
Publication restrictions are in place

Restriction type: OTHER