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

• ClinicalTrials.gov Identifier: NCT04093167
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2019
• Last Update Posted: April 11, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborators: 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: September 12, 2019
• First Posted Date: September 17, 2019
• Last Update Posted Date: April 11, 2023
• Actual Study Start Date: October 17, 2019
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

Drug: Pembrolizumab

200mg IV 2 mg/kg IV 400 mg IV 4 mg/kg IV

Study Arms

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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 16, 2019): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 30, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04093167
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current

Collaborators

• Cancer Research Institute, New York City
• Personal Genome Diagnostics (PGDx)
• Mark Foundation for Cancer Research

Investigators

• 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