There are 9 clinical trials
The investigators performed a multi-centered, randomized, double blinded, placebo-controlled, prospective clinical trial on the effect of Yiqi-yangyin-jiedu decoction (YYJD), a chinese herbal medicine (CHM) formula combined with gefitinib to prolong the progression free survival (PFS) of advanced pulmonary adenocarcinoma patients with activating EGFR mutation (exon19del or exon21L858R). The investigators plan to enroll 198 cases in 3 years (99 cases for gefitinib, 99 cases for gefitinib plus YYJD), expecting that combination therapy has a better efficacy on prolonging PFS, overall survival, improving quality of life(QOL).
Although AZD9291 (AstraZeneca), a third-generation EGFR-TKI is reported with a response rate of 61% in NSCLC patients with EGFR T790M and a mPFS of 9.6 months, resistance to third-generation inhibitors mediated by EGFR C797S mutation is inevitable. --- T790M --- --- C797S ---
Description: Time from start of the study treatment to date of objective tumour progression (excluding clinical deterioration without evidence of objective progression).
Measure: Progression-free survival (PFS) Time: 2 monthsDescription: interval time from the first date of randomization to that of death for any reason, the end of the study, or loss of follow-up
Measure: Overall survival (OS) Time: 2 monthsDescription: The ORR (complete response (CR) plus partial response (PR)) was determined by the Response Evaluation Criteria In Solid Tumors (RECIST) (Eisenhauer et al, 2009) version 1.1.in Solid Tumors (RECIST1.1).
Measure: Objective response rate (ORR) Time: 2 monthsDescription: QOL is assessed using Functional Assessment of Cancer therapy-lung (FACT-L) questionnaire .
Measure: Quality of life (QOL) Time: 2 monthsDescription: Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0).
Measure: Safety assessment evaluated according to Common Toxicity Criteria Time: 2 monthsThe third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.
Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---
Description: To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.
Measure: Objective Response Rate(ORR) according to resist 1.1 Time: 2yearsDescription: To evaluate the response to therapy and disease control rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.
Measure: disease control rate(DCR) according to resist 1.1 Time: 2yearsDescription: To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.
Measure: Time to progression(TTP) according to resist 1.1 Time: 2yearsDescription: To evaluate the response to therapy and duration of Response of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.
Measure: duration of Response(DOR) according to resist 1.1 Time: 2yearsThe third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.
Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---
Description: To evaluate the response to therapy and 1 year median progression-free survival（PFS） rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .
Measure: 1-year median progression-free survival（PFS） rates according to resist 1.1 Time: 3yearsDescription: To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .
Measure: median PFS according to resist 1.1 Time: 3yearsDescription: To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI
Measure: median overall survival(OS) according to resist 1.1 Time: 3yearsThis is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.
Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S ---
Description: Disease progression as defined by investigator assessments according to RECIST1.1
Measure: Proportion of acquired resistance mechanisms to osimertinib at disease progression Time: Through study completion, an average of 2 yearsDescription: AEs/SAEs as defined by NCI CTCAE version 5.0
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: Through study completion, an average of 2 yearsDescription: PFS as defined as the time from the date of initiation until the date of first documented progression
Measure: Progression-Free Survival (PFS) Time: Through study completion, an average of 2 yearsDescription: OS as defined as the time from the date of first dose until death due to any cause
Measure: Overall Survival (OS) Time: Through study completion, an average of 2 yearsDescription: ORR using investigator assessments according RECIST1.1
Measure: Objective Response Rate (ORR) Time: Through study completion, an average of 2 yearsThe study primary objective is to assess the concordance of T790M resistance mutation testing from hospital-based laboratories with T790M resistance mutation testing from a central laboratory.
The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing. --- C797S ---
Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S ---
Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S --- --- C797S ---
Description: Concordance (%)=(number of patients with same T790M mutation status based on central and local labs)/(total number of patients in the FAS) ×100%
Measure: the concordance of T790M mutation testing between the test in central and local labs Time: within 1 -14 days after enrolledDescription: Prevalence (%) = (number of patients with T790M mutation positive)/(total number of patients in the FAS)×100%
Measure: The prevalence rate of T790M mutation based on the central lab testing Time: within 1 -14 days after enrolledDescription: Sensitivity (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on tissue test) ×100%
Measure: The sensitivity of each platform based on the local lab plasma testing Time: within 1 -14 days after enrolledDescription: Specificity (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on tissue test) ×100%
Measure: The Specificity of each platform based on the local lab plasma testing Time: within 1 -14 days after enrolledDescription: Positive predictive value (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on plasma test) ×100%
Measure: The Positive predictive value of each platform based on the local lab plasma testing Time: within 1 -14 days after enrolledDescription: Negative predictive value (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on plasma test) ×100%
Measure: The Negative predictive value of each platform based on the local lab plasma testing Time: within 1 -14 days after enrolledDescription: Concordance (%)=(number of patients with same T790M mutation status based on tissue and plasma tests)/(total number of patients in the FAS) ×100%
Measure: The Concordance of each platform based on the local lab testing Time: within 1 -14 days after enrolledDescription: Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%
Measure: The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing Time: within 1 -14 days after enrolledDescription: Prevalence (%) = (number of patients with rare EGFR mutation positive)/(total number of patients in the FAS)×100%
Measure: Rare EGFR mutation prevalence rate Time: within 1-14 days after enrolledThe aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.
To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.. Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.. --- C797S ---
Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: 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: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1 Time: From first dose intake to Progression of disease (PD), up to 3 yearsDescription: To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and NGS platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing sensitivity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To assess the efficacy of AZD9291 monotherapy by assessment of ORR 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: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Objective Response Rate (ORR) Time: From first dose intake to end of study, up to 3 yearsDescription: To assess the efficacy of AZD9291 monotherapy by assessment of OS 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: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Overall Survival (OS) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing specificity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing positive predictive value (PPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing negative predictive value (NPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.
Measure: Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point. Time: every 6 weeks during treatment, up to 3 yearsDescription: To explore the mechanisms of acquired resistance in patients who received AZD9291 treatment by NGS testing of tissue and/or blood samples from the collection at PD versus baseline.
Measure: Changes of distribution of resistance related genes at PD compared with baseline. Time: every 6 weeks during treatment, up to 3 yearsDescription: To describe the genomic profile of long-term survivors, especially to find out potential genomic prognosis and/or predictive factors for AZD9291 long-term efficacy as compared to rapid PD patients.
Measure: Key genetic and proteomic markers including, but not limited to, EGFR mutations Time: every 6 weeks during treatment, up to 3 yearsDescription: To evaluate concordance of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing concordance Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate sensitivity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing sensitivity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate specificity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing specificity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate PPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing positive predictive value (PPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate NPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing negative predictive value (NPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Objective Response Rate (ORR) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Progression Free Survival (PFS) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Overall Survival (OS) Time: From first dose intake to end of study, up to 3 yearsBackground: Some non-small-cell lung cancers (NSCLC) have a mutation in a gene that makes a protein called EGFR. This particular cancer can be treated with certain drugs such as Erlotinib (Tarceva), Gefitinib (Iressa) and Osimertinib (Tagrisso). But many tumors become resistant to these drugs because of a second mutation. Researchers want to test if adding local ablative therapy (LAT) extends the benefits of the drug, Osimertinib. LAT can include techniques such as surgery, radiofrequency ablation, cryotherapy or radiation therapy. Objective: To test if re-taking osimertinib after LAT is safe, tolerable, and effective for people whose NSCLC has progressed after initial treatment with osimertinib. Eligibility: Adults ages 18 and older with certain types of NSCLC. Participants will be divided into various groups as described below. Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Tumor scans Eye exam Review of tumor sample. Participants will take the study drug by mouth once a day. They will continue until they can no longer tolerate it or their disease worsens. They will keep a dosage diary. All participants will start each 21-day course with physical exam; blood, urine, and saliva tests; and electrocardiogram. They will have scans every 6 weeks and echocardiogram every 3 months. Groups 1 and 2 will: Start osimertinib right away. Have LAT if their disease gets worse and is suitable for LAT. If LAT cannot be performed or LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Re-start osimertinib after LAT, or other treatments if not suitable for LAT. Group 3 will: Have LAT. If LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Start osimertinib after LAT. After participants stop taking the drugs, they will have a final visit. This will include: Medical history Physical exam Heart and blood tests Participants will be called every year for follow-up.
In fact, a newly identified EGFR mutation (C797S) that results in acquired resistance to osimertinib has been reported recently. --- C797S ---
Description: progression-free survival (PFS)
Measure: determine PFS in patients with oligoprogressive disease after treatment with LAT followed by osimertinib Time: progression of diseaseDescription: time to second progression (PFS2)
Measure: Patients who progress on their initial treatment with osimertinib and receive LAT therapy (surgery, radiation therapy, or RFA) followed by osimertinib will be evaluated for their time to second progression (PFS2) Time: progression of diseaseDescription: response rate
Measure: response rate Time: end of treatmentDescription: overall survival
Measure: overall survival Time: deathDescription: EGFR mutation status using liquid biopsies
Measure: feasibility of evaluating EGFR mutation status using liquid biopsies Time: end of treatmentThe purpose of this study is to evaluate the safety and pharmacokinetics, establish a recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).
Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). --- C797S ---
Description: The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.
Measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT) Time: Up to Day 28Description: An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measure: Number of Participants With Adverse Events (AEs) and Serious AEs Time: Screening up to follow-up (30 days after the last dose)Description: Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
Measure: Percentage of Participants With Clinical Benefit Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Description: Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
Measure: Overall Response Rate (ORR) Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Description: DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size ([<] 10 [mm] short axis) and normalisation of tumour marker levels) or PR (at least a 30 [%] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.
Measure: Duration of Response (DOR) Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Description: The Cmax is the maximum observed serum concentration of JNJ-61186372.
Measure: Maximum Serum Concentration (Cmax) of JNJ-61186372 Time: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months)Description: The Tmax is defined as time to reach maximum observed serum concentration of JNJ-61186372.
Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-61186372 Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: The AUC(t1-t2) is the area under the serum JNJ-61186372 concentration-time curve from time t1 to t2.
Measure: Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of JNJ-61186372 Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)
Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372 Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: The Ctrough is the observed serum concentration immediately prior to the next administration.
Measure: Trough Serum Concentration (Ctrough) of JNJ-61186372 Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.
Measure: Accumulation ratio (R) of JNJ-61186372 Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: Serum levels of antibodies to JNJ-61186372 for evaluation of potential immunogenicity.
Measure: Number of Participants With Anti-Drug Antibodies (ADA) Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)Description: PFS is defined as the time from first infusion of study drug to PD or death due to any cause.
Measure: Progression-Free Survival (PFS) Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Description: TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.
Measure: Time to Treatment Failure (TTF) Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Description: OS is defined as the time from first infusion of study drug to death due to any cause.
Measure: Overall Survival (OS) Time: Up to End of Treatment Follow Up Period (30 days after the last dose)Based on the possibilities that both plasma and circulating tumor cells (CTCs) (the "liquid biopsy") may offer, we consider that it could be feasible to longitudinally monitor the genetic evolution and the biologic characteristics of CTCs, by using Circulating tumor DNA (ctDNA) and CTCs as a source of biologic material. This approach could provide information regarding the genetic/molecular changes associated with primary and acquired resistance to AZD9291 and, thus, to facilitate to more appropriately adapt the tailored treatment in this particular group of NSCLC patients. It has been recently reported that the detection of resistant clones, based on the tumor-associated genetic aberrations in the blood, can identify treatment resistance up to 10 months earlier than the radiological methods providing, thus, the potential for an early switch to a non cross-resistant therapy in order to improve patients' outcome.
The patients will be followed every 3 months for the detection of mutations (T790M), (C797S), (L858R), del 19 EGFR mutations as well as the mutations [(KRAS)/(NRAS), (BRAF), (PI3K)] in the serum/plasma, the determination of the serum levels of Hepatocyte Growth Factor (HGF), the presence of T790M (+) and C797S(+) CTCs as well as the molecular (c-MET) and (HER2 amplification) and phenotypic characterization of CTCs using the filtration platform (ISET). --- T790M --- --- C797S ---