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Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04093167
Recruitment Status : Active, not recruiting
First Posted : September 17, 2019
Last Update Posted : April 11, 2023
Cancer Research Institute, New York City
Personal Genome Diagnostics (PGDx)
Mark Foundation for Cancer Research
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Tracking Information
First Submitted Date  ICMJE September 12, 2019
First Posted Date  ICMJE September 17, 2019
Last Update Posted Date April 11, 2023
Actual Study Start Date  ICMJE October 17, 2019
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2019)
Concordance rate between molecular response and radiologic response [ Time Frame: 18 months ]
Molecular response will be assessed by measuring changes in ctDNA levels in plasma
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2019)
  • Time to molecular response [ Time Frame: 18 months ]
  • Correlate molecular response to RECIST response based on changes in ctDNA levels [ Time Frame: 18 months ]
  • Correlate molecular response to progression-free survival based on changes in ctDNA levels [ Time Frame: 18 months ]
  • Correlate molecular response to overall survival based on changes in ctDNA levels [ Time Frame: 18 months ]
  • Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC
Official Title  ICMJE A Biomarker-Directed, Open Label, Multi-Centre Phase II Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With Non-Small Cell Lung Cancer
Brief Summary The purpose of stage 1 of the study is to find out if blood tests can be used to see how the cancer is responding to treatment with pembrolizumab.
Detailed Description

The standard or usual treatment for this disease is pembrolizumab given by needle every three weeks. This study will be done in two stages.

The purpose of stage 1 of the study is to find out if we can use blood tests to see how the cancer is responding to treatment with pembrolizumab. A second stage of the study will take place once stage 1 is completed. In stage 2 blood tests will be used to help determine if patients whose cancer does not seem to be getting better on treatment with pembrolizumab, would do better on a different treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: Pembrolizumab
200mg IV 2 mg/kg IV 400 mg IV 4 mg/kg IV
Study Arms  ICMJE Experimental: Pembrolizumab
200mg (or 2mg/kg) IV every 3 weeks for cycles 1-3 then as per standard of care for patients with PD-L1+ EGFR/ALK-NSCLC
Intervention: Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 16, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2024
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic NSCLC. Patients with stage III disease are eligible if they are not candidates for surgical resection or definitive chemoradiation. Patients with Large Cell Neuroendocrine Carcinoma (LCNEC) are not eligible.
  • Confirmed EGFR and ALK mutation-negative disease. Testing for EGFR and ALK is not required for patients with squamous histology.
  • Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1 expression Tumour Proportion Score (TPS) ≥ 1%.
  • No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed since the prior therapy and enrollment. Local therapy, e.g. palliative extra-cranial radiation, is allowed as long as a period of 2 weeks has passed since completion as ctDNA levels may be altered by radiotherapy. There is no requirement for delay for patients who have received brain radiation.
  • Patients must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic or radiation therapy.
  • Previous major surgery is permitted provided that surgery occurred at least 28 days prior to patient enrollment and that wound healing has occurred.
  • Eligible to receive treatment with pembrolizumab. Reimbursement of pembrolizumab may not be uniform across all sites. In the event that the site/investigator is unable to provide access to the drug, the patient will not be eligible for this trial.
  • Must be ≥ 18 years of age.
  • ECOG performance status 0 or 1.
  • Clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST 1.1.
  • Imaging investigations including CT of the chest, abdomen and pelvis and MRI of the brain (if known brain metastases) or other scans as necessary to document all sites of disease must be done within 28 days prior to enrollment.
  • Adequate hematology and organ function as defined below (must be done within 14 days prior to enrollment).

    • White Blood Cells ≥ 2.0 x 10^9/L (2000/μL)
    • Absolute neutrophils ≥ 1.5 x 10^9/L (1500/μL)
    • Platelets ≥ 100 x 10^9/L (100 x 10^3/μL)
    • Bilirubin ≤ 1.5 x ULN (upper limit of normal)*
    • AST and/or ALT ≤ 3 x ULN, < 5 x ULN for patients with liver metastases
    • Serum creatinine or Creatinine clearance ≤ 1.5 x ULN OR ≥ 40 mL/min
  • Patients must consent to provision of, and investigator must agree to submit, a representative archival formalin-fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available.
  • Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by CLIA central laboratory and for correlative analysis by a research central laboratory.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment to the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, collection of blood samples, response assessments and follow-up. Patients must agree to return to their primary care facility for response assessments as well as any adverse events which may occur through the course of the trial.
  • In accordance with CCTG policy, protocol treatment with pembrolizumab is to begin within 2 working days of patient enrollment.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation.

Exclusion Criteria:

  • Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with symptomatic central nervous system (CNS) metastases and/or CNS metastases requiring immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents). Patients with known central nervous system metastases who are asymptomatic and on a stable dose of corticosteroids ≤ 10 mg/day prednisone equivalents prior to enrollment are eligible.
  • Patients who are not suitable candidates for treatment with pembrolizumab according to the current guidance/indications described in the Product Monograph (Canada) or Drug Label (U.S.) including but not limited to patients with active infection, autoimmune disease, conditions that require systemic immunosuppressive therapy (such as transplant patients) and patients with a history of severe immune-mediated adverse reactions, or known hypersensitivity to pembrolizumab or its components. Patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders (such as hypo or hyperthyroidism or diabetes mellitus), can be considered for enrollment to this study provided pembrolizumab is administered with caution and patients are closely monitored
  • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
  • Concurrent treatment with other anti-cancer therapy or other investigational anti-cancer agents
  • Pregnant or lactating women.
  • Men who are sexually active with women of childbearing potential and women of childbearing potential must agree to use adequate contraception.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04093167
Other Study ID Numbers  ICMJE BR36
CRI-CCTG-002 ( Other Identifier: CRI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Canadian Cancer Trials Group
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Canadian Cancer Trials Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Cancer Research Institute, New York City
  • Personal Genome Diagnostics (PGDx)
  • Mark Foundation for Cancer Research
Investigators  ICMJE
Study Chair: Valsamo Anagnostou Johns Hopkins University
Study Chair: Cheryl Ho BCCA - Vancouver Cancer Centre
PRS Account Canadian Cancer Trials Group
Verification Date April 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP