Trial Outcomes & Findings for T790M Plasma Testing Methodology Comparison and Clinical Validation (NCT NCT02997501)

Last Updated: 2024-03-04

Results Overview

To evaluate concordance of T790M plasma mutation testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

256 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2024-03-04

Participant Flow

1. Provision of informed consent prior to any study specific procedures. 2. Adults (according to China regulations for age of majority). 3. Histological or cytological confirmed locally advanced NSCLC (stage IIIB) or metastatic (stage IV) NSCLC, not amenable to curative surgery or radiotherapy. 4. Patients who have progressed following prior therapy with an EGFR-TKI agent.

subjects with T790M+ in plasma were treated by AZD9291 and included in as-treated analysis set

Participant milestones

Participant milestones
Measure	Experimental Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
Overall Study STARTED	256
Overall Study COMPLETED	256
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

T790M Plasma Testing Methodology Comparison and Clinical Validation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental n=256 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
Age, Continuous	58.54 years STANDARD_DEVIATION 9.506 • n=99 Participants
Sex: Female, Male Female	160 Participants n=99 Participants
Sex: Female, Male Male	96 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	256 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
enrollment number Patients who have progressed following prior therapy with an EGFR-TKI agent.	256 Participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 6 months

To evaluate concordance of T790M plasma mutation testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS.

Outcome measures

Outcome measures
Measure	Experimental n=256 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
Concordance For T790M, referred to Super-ARMS, the concordance for ddPCR	88.1 percentage of aggrement
Concordance For T790M, referred to Cobas, the concordance for Super-ARMS	91.3 percentage of aggrement
Concordance For T790M, referred to Cobas, the concordance for 3D PCR	66.8 percentage of aggrement
Concordance For T790M, referred to Cobas, the concordance for NGS	82.7 percentage of aggrement
Concordance For T790M, referred to Cobas, the concordance for ddPCR	86.1 percentage of aggrement
Concordance For T790M, referred to Super-ARMS, the concordance for 3D PCR	71.0 percentage of aggrement
Concordance For T790M, referred to Super-ARMS, the concordance for NGS	88.3 percentage of aggrement
Concordance For T790M, referred to 3D PCR, the concordance for NGS	76.5 percentage of aggrement
Concordance For T790M, referred to 3D PCR, the concordance for ddPCR	72.2 percentage of aggrement
Concordance For T790M, referred to NGS, the concordance for ddPCR	85.8 percentage of aggrement

PRIMARY outcome

Timeframe: The time from first dose of AZD9291 in this study until the date of disease progression as recorded in CRF or death (by any cause in the absence of progression), assessed up to 18 months

Population: Analysis population included AS-treated Analysis Set which contains all T790M postive patients via at least one of platforms. Patients with T790M positive results tested by each platform were also analyzed.

To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms. PFS was defined using Response Evaluation Criteria In Solid Tumors version 1.1(RECIST v1.1).

Outcome measures

Outcome measures
Measure	Experimental n=167 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
PFS Using Investigator Assessments According to RECIST v1.1 As-treated Analysis Set (contained all patients who took at least one dose of AZD9291)	9.7 months Interval 8.4 to 11.2
PFS Using Investigator Assessments According to RECIST v1.1 T790M Positive in Plasma via Cobas at Baseline	10.6 months Interval 8.5 to 13.8
PFS Using Investigator Assessments According to RECIST v1.1 T790M Positive in Plasma via Super-ARMS at Baseline	10.6 months Interval 8.7 to 12.5
PFS Using Investigator Assessments According to RECIST v1.1 T790M Positive in Plasma via 3D PCR at Baseline	9.7 months Interval 8.3 to 11.3
PFS Using Investigator Assessments According to RECIST v1.1 T790M Positive in Plasma via NGS at Baseline	11.0 months Interval 9.5 to 13.8
PFS Using Investigator Assessments According to RECIST v1.1 T790M Positive in Plasma via ddPCR at Baseline	10.5 months Interval 8.3 to 12.7

SECONDARY outcome

Timeframe: Up to 6 months.

To evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Outcome measures

Outcome measures
Measure	Experimental n=256 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
Testing Sensitivity, Specificity, PPV, NPV sensitivity for Super-ARMS	94.7 percentage
Testing Sensitivity, Specificity, PPV, NPV sensitivity for 3D PCR	90.5 percentage
Testing Sensitivity, Specificity, PPV, NPV sensitivity for NGS	98.9 percentage
Testing Sensitivity, Specificity, PPV, NPV sensitivity for ddPCR	98.9 percentage
Testing Sensitivity, Specificity, PPV, NPV specificity for Super-ARMS	89.3 percentage
Testing Sensitivity, Specificity, PPV, NPV specificity for 3D PCR	52.5 percentage
Testing Sensitivity, Specificity, PPV, NPV specificity for NGS	73.0 percentage
Testing Sensitivity, Specificity, PPV, NPV specificity for ddPCR	78.5 percentage
Testing Sensitivity, Specificity, PPV, NPV PPV for Super-ARMS	84.1 percentage
Testing Sensitivity, Specificity, PPV, NPV PPV for 3D PCR	53.4 percentage
Testing Sensitivity, Specificity, PPV, NPV PPV for NGS	68.6 percentage
Testing Sensitivity, Specificity, PPV, NPV PPV for ddPCR	73.0 percentage
Testing Sensitivity, Specificity, PPV, NPV NPV for Super-ARMS	96.6 percentage
Testing Sensitivity, Specificity, PPV, NPV NPV for 3D PCR	90.2 percentage
Testing Sensitivity, Specificity, PPV, NPV NPV for NGS	99.1 percentage
Testing Sensitivity, Specificity, PPV, NPV NPV for ddPCR	99.2 percentage

SECONDARY outcome

Timeframe: From first patient first CT scan for RECIST assessment, till the last patient last CT scan, up to 22 months.

To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients who have received prior EGFR-TKI therapy and are EGFR T790M mutation positive detected by any one of the four plasma testing platforms. ORR is defined as the percentage of patients with measurable disease with at least 1 visit response of CR or PR. Data obtained until progression or last evaluable assessment in the absence of progression will be included in the assessment of ORR.

Outcome measures

Outcome measures
Measure	Experimental n=167 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
Overall Response Rate (ORR) As-treated Analysis Set	56.3 percentage of participants Interval 48.4 to 63.9
Overall Response Rate (ORR) T790M Positive in Plasma via Cobas at Baseline	60.7 percentage of participants Interval 49.7 to 70.9
Overall Response Rate (ORR) T790M Positive in Plasma via Super-ARMS at Baseline	62.4 percentage of participants Interval 52.2 to 71.8
Overall Response Rate (ORR) T790M Positive in Plasma via 3D PCR at Baseline	54.1 percentage of participants Interval 45.7 to 62.3
Overall Response Rate (ORR) T790M Positive in Plasma via NGS at Baseline	62.0 percentage of participants Interval 53.1 to 70.4
Overall Response Rate (ORR) T790M Positive in Plasma via ddPCR at Baseline	59.1 percentage of participants Interval 49.3 to 68.4

SECONDARY outcome

Timeframe: From first patient signed the consent to study completion, up to 22 months.

To assess the efficacy of AZD9291 monotherapy by assessment of overall survival (OS) in adult patients who have received prior EGFR-TKI therapy and are EGFR T790M mutation positive detected by any one of the four plasma testing platforms. 75% OS duration was calculated.

Outcome measures

Outcome measures
Measure	Experimental n=167 Participants Patients who have progressed on previous EGFR-TKI receiving AZD9291 80mg PO QD.
75% OS Duration T790M Positive in Plasma via Super-ARMS at Baseline	10.7 months Interval 8.0 to 14.5
75% OS Duration As-treated Analysis Set	9.7 months Interval 7.5 to 12.7
75% OS Duration T790M Positive in Plasma via Cobas at Baseline	10.5 months Interval 7.3 to 13.6
75% OS Duration T790M Positive in Plasma via 3D PCR at Baseline	8.7 months Interval 7.3 to 12.1
75% OS Duration T790M Positive in Plasma via NGS at Baseline	11.9 months Interval 8.7 to 15.3
75% OS Duration T790M Positive in Plasma via ddPCR at Baseline	10.6 months Interval 8.0 to 14.3

Adverse Events

Experimental

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Global Clinical Lead

Astrazeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place