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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04685135

Registration number

NCT04685135

Ethics application status

Date submitted

21/12/2020

Date registered

28/12/2020

Date last updated

25/03/2025

Titles & IDs

Public title

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

Scientific title

A Randomized Phase 3 Study of MRTX849 Versus Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation

Secondary ID [1]

CA239-0013

Secondary ID [2]

CA239-0013

Universal Trial Number (UTN)

Trial acronym

KRYSTAL-12

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Metastatic Non Small Cell Lung Cancer

Advanced Non Small Cell Lung Cancer

Condition category

Condition code

Cancer

Lung - Mesothelioma

Cancer

Lung - Non small cell

Cancer

Lung - Small cell

Intervention/exposure

Study type

Interventional(has expanded access)

Description of intervention(s) / exposure

Treatment: Drugs - MRTX849
Treatment: Drugs - Docetaxel

Experimental: MRTX849 -

Active comparator: Docetaxel -

Treatment: Drugs: MRTX849
21 day cycles

Treatment: Drugs: Docetaxel
21 day cycles

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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

Assessment method [1]

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.

Timepoint [1]

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

Secondary outcome [1]

Overall Survival (OS)

Assessment method [1]

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

Timepoint [1]

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

Secondary outcome [2]

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

Assessment method [2]

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.

Timepoint [2]

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)

Secondary outcome [3]

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

Assessment method [3]

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.

Timepoint [3]

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)

Secondary outcome [4]

1-Year Survival Rate

Assessment method [4]

Timepoint [4]

Up to 49 months

Secondary outcome [5]

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Assessment method [5]

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.

Timepoint [5]

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

Secondary outcome [6]

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

Assessment method [6]

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.

Timepoint [6]

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

Secondary outcome [7]

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

Assessment method [7]

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.

Timepoint [7]

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

Secondary outcome [8]

Plasma Concentration of Adagrasib

Assessment method [8]

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.

Timepoint [8]

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)

Secondary outcome [9]

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

Assessment method [9]

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.

Timepoint [9]