Study of CTDNA Response Adaptive Immuno-Chemotherapy in Lung Cancer

NCT04093167 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: BR36CRI-CCTG-002
• Study Type: interventional
• Target: 230
• Locations: 2 countries
• Sites: 10

Brief 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 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.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (3)

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

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

  18 months

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

  3 years

• Stage 2: Phase III Overall Survival

  3 years

Secondary Outcomes (14)

• Stage 1: Time to molecular response

  18 months

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

  18 months

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

  18 months

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

  18 months

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

  18 months

Study Arms (2)

Pembrolizumab alone

ACTIVE COMPARATOR

Drug: Pembrolizumab

Pembrolizumab + standard platinum-based chemotherapy

EXPERIMENTAL

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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

Pembrolizumab + standard platinum-based chemotherapy; Pembrolizumab alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Cancer Research Institute, New York City: collaborator
• Personal Genome Diagnostics: collaborator
• Mark Foundation for Cancer Research: collaborator

Study Sites (10)

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

The Sidney Kimmel Comprehensive Cancer Centre

Baltimore, Maryland, 21231, United States

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 37814061 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Valsamo Anagnostou

  Johns Hopkins University

  STUDY CHAIR

• Sara Moore

  Ottawa Hospital Research Institute

  STUDY CHAIR

Central Study Contacts

Janet Dancey

CONTACT

613-533-6430; jdancey@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 17, 2019
• Study Start: May 26, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8); US (2)