Study of CTDNA Response Adaptive Immuno-Chemotherapy in NSCLC
NCT ID: NCT04093167
Last Updated: 2025-12-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2/PHASE3
230 participants
INTERVENTIONAL
2020-05-26
2027-07-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Pembrolizumab alone
Pembrolizumab
Per current Product Monograph/U.S. Drug Label and/or local guidelines.
Pembrolizumab + standard platinum-based chemotherapy
Pembrolizumab
Per current Product Monograph/U.S. Drug Label and/or local guidelines.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pembrolizumab
Per current Product Monograph/U.S. Drug Label and/or local guidelines.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Confirmed EGFR and ALK mutation-negative disease based on testing consistent with local guidelines.
* Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1 expression Tumour Proportion Score (TPS) ≥ 50%. Patients with lower PD-L1 TPS scores treated with single agent pembrolizumab consistent with local guidelines and regulatory approvals may be eligible following discussion with CCTG.
* Patients are to be registered prior to starting immunotherapy. Screening ctDNA is to be drawn following registration prior to starting immunotherapy and after not more than 2 cycles of the 200mg or 2mg/kg IV Q3W dose/schedule of pembrolizumab, or at least and not more than 1 cycle of 400mg or 4mg/kg IV Q6W dose/schedule of pembrolizumab as first-line systemic immunotherapy for advanced metastatic NSCLC at the time of. Eligible patients with detectable ctDNA at 6 weeks may proceed to enrollment and randomization.
* Prior chemotherapy or immunotherapy for non-metastatic disease (e.g. adjuvant and or neoadjuvant therapy) is allowed if at least 6 months have elapsed between the completion of prior therapy and start of pembrolizumab as first-line treatment for metastatic disease. Local therapy, e.g. palliative extra-cranial radiation, is allowed as long as a period of 2 weeks has passed since completion and screening 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 14 days prior to screening of ctDNA and 28 days prior to patient enrollment and that wound healing has occurred.
* Eligible and suitable to receive continued treatment with pembrolizumab OR the addition of chemotherapy to pembrolizumab at the time of registration and again at the time of enrollment and randomization. Patients should be clinically stable without evidence of clinical progression or symptomatic deterioration that requires change in cancer treatment. 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 0-2.
* Clinically and/or radiologically documented and evaluable disease. Measurable disease as defined by RECIST is not required.
* Imaging investigations including CT of the chest, abdomen and pelvis and MRI/CT of the brain (if known brain metastases) or other scans as necessary to document all sites of disease must be done within 14 days prior to randomization to ensure patients do not have clinical progression requiring change in systemic treatment. Patients must have non-progression of disease to be randomized. Patients who are clinically stable with PD such that in the opinion of the investigator they could continue with single agent immunotherapy may be eligible for enrollment and randomization following discussion with CCTG.
* Patients must have RECIST non-PD or clinically stable PD documented prior to enrollment that can continue on IO therapy if randomized to that arm.
* Detectable ctDNA on screening at 6 weeks is required for subsequent enrollment and randomization.
* Adequate hematology and organ function to continue immunotherapy or receive standard platinum combination therapy (must be done prior to registration for ctDNA testing) and prior to enrollment and randomization).
* 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 the 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.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to registration to the trial to document their willingness to the collection of liquid biopsy (blood) samples for ctDNA analysis by CLIA central laboratory and for correlative analysis by a research central laboratory, and to subsequent enrollment and randomization to continued pembrolizumab or the addition of chemotherapy to pembrolizumab if ctDNA is detected.
* 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 is to begin within 5 working days of patient randomization.
* Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during protocol treatment and for at least 6 months after the last dose of the protocol treatment. Participants of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation. Male participants with partners of childbearing potential must agree to use condoms (with spermicide, if available) in combination with an additional highly effective contraceptive method used by their partner, during treatment period and for at least 6 months after the last dose of the investigational product.
Exclusion Criteria
* 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 are eligible.
* Patients who are not suitable candidates for treatment with pembrolizumab as a single agent or in combination with standard platinum combination chemotherapy according to the current guidance/indications described in the Product Monograph (Canada) or Drug Label (U.S.) and practice guidelines 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. Patients should not have contraindications to platinum combination chemotherapy.
* History of significant neurologic or psychiatric disorder that 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Cancer Research Institute, New York City
OTHER
Personal Genome Diagnostics
INDUSTRY
Mark Foundation for Cancer Research
UNKNOWN
Canadian Cancer Trials Group
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Valsamo Anagnostou
Role: STUDY_CHAIR
Johns Hopkins University
Sara Moore
Role: STUDY_CHAIR
Ottawa Hospital Research Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
The Sidney Kimmel Comprehensive Cancer Centre
Baltimore, Maryland, United States
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
Kingston, Ontario, Canada
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Valsamo Anagnostou
Role: primary
Cheryl Ho
Role: primary
Rosalyn Anne Juergens
Role: primary
Andrea Fung
Role: primary
Garth Nicholas
Role: primary
Adrian Sacher
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
Anagnostou V, Ho C, Nicholas G, Juergens RA, Sacher A, Fung AS, Wheatley-Price P, Laurie SA, Levy B, Brahmer JR, Balan A, Niknafs N, Avrutin E, Zhu L, Sausen M, Bradbury PA, O'Donnell-Tormey J, Gaudreau PO, Ding K, Dancey J. ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. Nat Med. 2023 Oct;29(10):2559-2569. doi: 10.1038/s41591-023-02598-9. Epub 2023 Oct 9.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CRI-CCTG-002
Identifier Type: OTHER
Identifier Source: secondary_id
BR36
Identifier Type: -
Identifier Source: org_study_id