NCT04685135 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-11

This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS) as Per Blinded Independent Central Review

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · POSTED

Objective Response Rate (ORR) as Per Blinded Independent Central Review

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outcome · POSTED

Duration of Response (DOR) as Per Blinded Independent Central Review

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outcome · NOT POSTED

1-Year Survival Rate

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outcome · POSTED

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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outcome · POSTED

Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters

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outcome · POSTED

Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters

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outcome · POSTED

Plasma Concentration of Adagrasib

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outcome · POSTED

Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Total Score

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outcome · POSTED

Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index Score

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outcome · POSTED

Change From Baseline in Lung Cancer Symptom Scale (LCSS) 3-Item Global Index Score

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outcome · POSTED

Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Visual Analogue Scale Score

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outcome · POSTED

Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Health Utility Index Score

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation. * Candidacy to receive treatment with docetaxel. Crossover Inclusion Criteria: * Evidence of RECIST 1.1 defined disease progression on docetaxel per BICR * ECOG performance status 0-2 Exclusion Criteria: * Prior treatment with an agent targeting KRAS G12C (e.g., AMG 510, Sotorasib). * Active brain metastases. Crossover Exclusion Criteria: * Receipt of any other systemic anti-cancer therapy after last administration of docetaxel on the study.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: MRTX849
label
MRTX849
type
EXPERIMENTAL
intervention Names
Drug: Docetaxel
label
Docetaxel
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
MRTX849
description
21 day cycles
name
MRTX849
other Names
adagrasib
KRAZATI
type
DRUG
arm Group Labels
Docetaxel
description
21 day cycles
name
Docetaxel
other Names
Taxotere
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 453
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression-Free Survival (PFS) as Per Blinded Independent Central Review
time Frame
From randomization to the date of progression or death due to any cause, whichever occurs first (up to approximately 143 weeks)

secondary Outcomes

description
Overall survival is defined as the time from randomization to the date of death due to any cause.
measure
Overall Survival (OS)
time Frame
From randomization till death due to any cause (up to approximately 143 weeks)
description
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.
measure
Objective Response Rate (ORR) as Per Blinded Independent Central Review
time Frame
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)
description
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.
measure
Duration of Response (DOR) as Per Blinded Independent Central Review
time Frame
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)
measure
1-Year Survival Rate
time Frame
Up to 49 months
description
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.
measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
time Frame
From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)
description
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.
measure
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Hematology Parameters
time Frame
From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)
description
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.
measure
Number of Participants With Maximum CTCAE Grade Laboratory Abnormality in Chemistry Parameters
time Frame
From first dose of treatment (Day 1) till 28 days after last dose (Up to approximately 110 weeks)
description
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.
measure
Plasma Concentration of Adagrasib
time Frame
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)
description
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.
measure
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Total Score
time Frame
Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)
description
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.
measure
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index Score
time Frame
Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)
description
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.
measure
Change From Baseline in Lung Cancer Symptom Scale (LCSS) 3-Item Global Index Score
time Frame
Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)
description
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.
measure
Change From Baseline at End of Treatment in European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) Visual Analogue Scale Score
time Frame
Baseline (Day 1) and up to End of Treatment (Up to approximately 106 weeks)

Full study description

brief Summary: This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation.

Source references

references

citation
Barlesi F, Yao W, Duruisseaux M, Doucet L, Martinez AA, Gregorc V, Juan-Vidal O, Lu S, De Bondt C, de Marinis F, Linardou H, Kim YC, Jotte R, Felip E, Lo Russo G, Reck M, Michenzie MF, Yang W, Meade JN, Korytowsky B, Mok TSK; KRYSTAL-12 Investigators. Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet. 2025 Aug 9;406(10503):615-626. doi: 10.1016/S0140-6736(25)00866-9.
pmid
40783289
type
DERIVED