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NCT02949843

Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations

Terminated Phase 2 Results posted Last updated 28 June 2024
What this trial tests

Phase 2 trial testing Chemotherapy in EGFR Activating Mutation in 19 participants. Terminated before completion.

Timeline
10 March 2017
Primary endpoint
8 January 2018
12 January 2021

Quick facts

Lead sponsorWake Forest University Health Sciences
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment19
Start date10 March 2017
Primary completion8 January 2018
Estimated completion12 January 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Wake Forest University Health Sciences

Who can join

Eligibility, any sex, with EGFR Activating Mutation or Recurrent Non-Small Cell Lung Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate in Patients With High PD-L1 Expressing Cancers After Failure of Targeted Therapy Defined as Complete or Partial Response According to the Investigator's Assessment Primary · Up to 1 year after failure of targeted therapy

Objective Response is defined as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). This outcome applies only to Arm I. \* Complete Response (CR): Disappearance of all target lesions, \* Partial Response (PR): At least a 30% decrease in the sum of the target lesions Progressive Disease (PD): At least a 20% increase in the sum of the target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease

GroupValue95% CI
Arm I (Nivolumab, Pembrolizumab)1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)0
Arm I (Nivolumab, Pembrolizumab)0
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)0
Number of Participants With Adverse Events Measured Using Common Terminology Criteria for Adverse Events Version 4.0 Secondary · Adverse events were collected following each cycle of treatment (1-4) and up to 30 days after the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks.

Toxicities for each group will be estimated and described using counts and frequencies by grade, location and relatedness.

GroupValue95% CI
Arm I (Nivolumab, Pembrolizumab)1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)1
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)3
Number of Mutations in Secondary Genes for Patients With PD-L1 Expression < 50% Secondary · Up to 1 year after failure of targeted therapy

This outcome applies to only Arms II and III.

GroupValue95% CI
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)2
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)0
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)2
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)1
Objective Response Rates for Patients Without High PD-L1 Expressing Cancers Secondary · Up to 3 years after failure of targeted therapy

Objective response rates will be estimated in the two PD-L1 expression \< 50% arms. At the time of protocol development, the intention was to estimate confidence intervals for each of these rates, and to make an exploratory comparison among the three groups comparing complete response/partial response versus stable disease/progressive disease among the groups using a Fisher's exact test (for the 2x3 table). Due to the low numbers of patients evaluable for response, these analyses were not performed.

GroupValue95% CI
Arm I (Nivolumab, Pembrolizumab)1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)1
Arm I (Nivolumab, Pembrolizumab)0
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)1
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)1
Overall Survival Secondary · From date of progression on primary targeted treatment to death, assessed up to 3 years.

Estimated using Kaplan-Meier methods and survival rates will be compared using log-rank tests. Note: Log-rank tests will not be used due to the very low sample size.

GroupValue95% CI
Arm I (Nivolumab, Pembrolizumab)3636 – 36
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)8.30.72 – 15.94
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)2.561.08 – 36
Rate of Tobacco Use and Mutation Burden Based on PD-L1 Expression at Time of Progression Secondary · Assessed at enrollment into study.

Smoking History was defined as Never, Former or Current

GroupValue95% CI
Arm I (Nivolumab, Pembrolizumab)1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)2
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)1
Arm I (Nivolumab, Pembrolizumab)0
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)2
Arm I (Nivolumab, Pembrolizumab)0
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)0
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected following each cycle of treatment (1-4), and up to 30 days following the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks. One patient refused additional treatment after the initial progression and was not followed for adverse events, but was followed for mortality.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Nivolumab, Pembrolizumab)
Serious: 0/1 (0%)
Deaths: 0/1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)
Serious: 1/1 (100%)
Deaths: 2/2
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)
Serious: 2/3 (67%)
Deaths: 2/3

Serious adverse events (7 terms)

ReactionSystemArm I (Nivolumab, Pembroli…Arm II (Kinase Inhibitor, …Arm III (Kinase Inhibitor,…
DyspneaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Creatinine increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
Cardiac arrestCardiac disorders
SepsisInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
Other adverse events (40 terms — click to expand)

ReactionSystemArm I (Nivolumab, Pembroli…Arm II (Kinase Inhibitor, …Arm III (Kinase Inhibitor,…
FeverGeneral disorders
Alkaline phosphatase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
HypercalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HypermagnesemiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
DiarrheaGastrointestinal disorders
FatigueGeneral disorders
Lymphocyte count decreasedInvestigations
HypernatremiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
LeukocytotsisBlood and lymphatic system disorders
PalpitationsCardiac disorders
NauseaGastrointestinal disorders
ColitisGastrointestinal disorders
HemorrhoidsGastrointestinal disorders
PainGeneral disorders
Lung InfectionInfections and infestations
FractureInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
CD4 lymphocytes decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
AnorexiaMetabolism and nutrition disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Chronic kidney diseaseRenal and urinary disorders
HematuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pulmonary edemaRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Dyspnea, Respiratory failure, Creatinine increased, Hypoalbuminemia, Cardiac arrest, Sepsis, Pneumonitis.

Data from ClinicalTrials.gov NCT02949843 adverse events section.

Sponsor's own description

This phase II trial studies how well targeted therapy works in treating patients with incurable non-small cell lung cancer with a genetic mutation. Giving drugs that target other genetic mutations or other specific proteins may work better when a patient has cancer caused by a driver mutation and the treatment that targets that mutation stops working.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.
    Chan TA, Yarchoan M, Jaffee E, Swanton C, et al · · 2019 · cited 2009× · PMID 30395155 · DOI 10.1093/annonc/mdy495
  2. Immunological features of EGFR-mutant non-small cell lung cancer and clinical practice: a narrative review.
    Dong Y, Khan L, Yao Y. · · 2024 · cited 13× · PMID 39735443 · DOI 10.1016/j.jncc.2024.06.004

Verify or expand the search:

Other trials of Chemotherapy

Trials testing the same drug.

Other recruiting trials for EGFR Activating Mutation

Currently open trials in the same condition.

Other Wake Forest University Health Sciences trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02949843.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing