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Lung CancerPhase 2/3NCT04093167

Study of CTDNA Response Adaptive Immuno-Chemotherapy in Lung Cancer

A Phase 2/3 study testing Pembrolizumab in people with Lung Cancer, run by Canadian Cancer Trials Group at 11 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The standard or usual treatment for this disease is pembrolizumab given by needle into the veins (IV). Some cancers shed DNA (circulating tumour DNA or ctDNA) or genes (biomarkers) into the blood, and levels of these biomarkers may be able to tell researchers how people respond to treatment with pembrolizumab before… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
11 sitesin 2 countries
Study dates
26 May 2020to 30 Jul 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 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.
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  • 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.

Who cannot join

  • 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 protocol treatment regimens 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 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.

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

Canada9 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Health Sciences North

    Greater Sudbury, Ontario, P3E 5J1

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • The Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

United States2 sites

  • The Sidney Kimmel Comprehensive Cancer Centre

    Baltimore, Maryland, 21231

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: A Biomarker-Directed, Multi-Centre Phase II/III Study of CTDNA Response Adaptive Immuno-Chemotherapy in Lung Cancer

The standard or usual treatment for this disease is pembrolizumab given by needle into the veins (IV).

Some cancers shed DNA (circulating tumour DNA or ctDNA) or genes (biomarkers) into the blood, and levels of these biomarkers may be able to tell researchers how people respond to treatment with pembrolizumab before they feel worse, or the cancer is worse on imaging tests. Researchers are studying how levels of these biomarkers can show how cancers are responding to treatment and whether adding chemotherapy to pembrolizumab based on detection of ctDNA can offer better results.

Read the detailed description

This study is being done in two stages. Participants are being invited to participate in stage 2. The purpose of stage 1 of the study was to find out how soon ctDNA disappears from blood in patients with lung cancer treated with pembrolizumab and whether ctDNA disappearance or continued detection related to how well people did.

In stage 2 the study will use the blood tests to figure out if patients on treatment with pembrolizumab with ctDNA that is still detected in the blood after 6 weeks of pembrolizumab could do better by adding standard chemotherapy treatment before the cancer is worse compared to continuing on standard pembrolizumab without added chemotherapy.

Conditions
Lung Cancer
Being tested
Pembrolizumab
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Per current Product Monograph/U.S. Drug Label and/or local guidelines.

Study groups in NCT04093167
Study groupRoleWhat they receive
Pembrolizumab aloneActive comparatorNot described
Receives: Drug: Pembrolizumab
Pembrolizumab + standard platinum-based chemotherapyExperimentalNot described
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Stage 1: Concordance rate between molecular response and radiologic response

    Molecular response will be assessed by measuring changes in ctDNA levels in plasma

    Measured: 18 months

  2. Stage 2: Phase II Progression-Free Survival (PFS)

    Measured: 3 years

  3. Stage 2: Phase III Overall Survival

    Measured: 3 years

Secondary outcomes (14)

  1. Stage 1: Time to molecular response

    Measured: 18 months

  2. Stage 1: Correlate molecular response to RECIST response based on changes in ctDNA levels

    Measured: 18 months

  3. Stage 1: Correlate molecular response to progression-free survival based on changes in ctDNA levels

    Measured: 18 months

  4. Stage 1: Correlate molecular response to overall survival based on changes in ctDNA levels

    Measured: 18 months

  5. Stage 1: Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma

    Measured: 18 months

  6. Stage 2: Phase II - Feasibility defined as screening success greater than 30% of patients screened have persistent ctDNA post 6 weeks of pembrolizumab

    Measured: 3 years

  7. Stage 2: Phase II - Feasibility defined as accrual reaching 50% of project accrual by month 18 post randomization

    Measured: 3 years

  8. Stage 2: Phase II - Feasibility defined as acceptance of randomization defined as >/= 80% of consenting patients accept randomization

    Measured: 3 years

  9. Stage 2: Phase II - clinical efficacy endpoints of best overall response rate post randomization

    Measured: 3 years

  10. Stage 2: Phase II - Number and severity of adverse events assessed by CTCAE v5

    Measured: 3 years

  11. Stage 2: Phase III - Clinical efficacy endpoints of best overall RECIST response rate post-randomization

    Measured: 3 years

  12. Stage 2: Phase III - Clinical efficacy endpoints of response duration

    Measured: 3 years

  13. Stage 2: Phase III - Clinical efficacy endpoints of progression-free survival

    Measured: 3 years

  14. Stage 2: Phase III - Number and severity of adverse events assessed by CTCAE v5

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2019
  2. Study start26 May 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion30 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04093167
Sponsor's protocol ID
BR36
Other IDs
CRI-CCTG-002
Status last verified
Jul 2026
First submitted
12 Sep 2019
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37814061

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Pembrolizumab in people with Lung Cancer, run by Canadian Cancer Trials Group at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Stage 1: Concordance rate between molecular response and radiologic response (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04093167, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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