Study of Nivolumab-Ipilimumab and cfDNA in Lung Cancer

NCT04966676 | Terminated Phase 2 DMC

• 1 other identifier: ATLAS
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to look at how effective two drugs, nivolumab and ipilimumab, are for people with non-small lung cancer that has metastasized (has spread to other parts of the body) and to see what effects these drugs have on these tumors.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of participants whose disease does not worsen (progression-free survival rate) at 6 months

  Progression-free survival (PFS) and 6-month PFS rate, as per RECIST 1.1, will be estimated using the Kaplan-Meier method together with their 95% confidence limit. The PFS of the study cohort will be compared to the historical controls derived from the CM9LA study.

  6 months

Secondary Outcomes (4)

• Average percentage of tumor cfDNA detected in the blood (tumor cfDNA clearance rate) at 3 weeks

  3 weeks

• Average percentage of tumor cfDNA detected in the blood (tumor cfDNA clearance rate) at 12 weeks

  12 weeks

• Number participants with adverse events

  4 years

• Average time from the date of study enrolment until death (overall survival)

  4 years

Study Arms (1)

Non-Small cell Lung Cancer

EXPERIMENTAL

Nivolumab, intravenously (given by vein), once every 3 weeks Ipilimumab, intravenously (given by vein), once every 6 weeks Participants will have blood samples taken for cell free deoxyribonucleic acid (cfDNA) testing. If there is an increasing or stable tumor cfDNA, platinum-doublet chemotherapy will be given.

Diagnostic Test: cfDNA blood test; Drug: Nivolumab; Drug: Ipilimumab; Combination Product: Platinum-based Chemotherapy

Interventions

Ipilimumab DRUG

Antineoplastic agent

Also known as: BMS-734016, MDX010, MDX-CTLA4

Non-Small cell Lung Cancer

Platinum-based Chemotherapy COMBINATION_PRODUCT

May include carboplatin with gemcitabine, or paclitaxel or pemetrexed

Non-Small cell Lung Cancer

cfDNA blood test DIAGNOSTIC_TEST

Blood sample will be taken for cfDNA testing

Non-Small cell Lung Cancer

Nivolumab DRUG

Antineoplastic agent

Also known as: Opdivo®, BMS-936558 or MDX1106

Non-Small cell Lung Cancer

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of screening or age of consent.
• Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Weight ≥ 35 kg.
• Must have a life expectancy of at least 12 weeks.
• Recurrent or newly diagnosed metastatic non-small cell lung cancer
• Tumor PDL1 status \<50%.
• Non-Squamous and squamous histologies are eligible
• Histologies with targetable mutations (EGFR, ALK, ROS1) are not eligible, regardless of prior treatment with tyrosine kinase inhibitors
• No prior radiation, surgery or chemotherapy is allowed for the current diagnosis of non-small cell lung cancer
• Adequate organ and marrow function

You may not qualify if:

• Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment.
• Prior receipt of any immune-mediated therapy.
• Incomplete surgical resection
• Concurrent enrolment in another therapeutic clinical study. Enrolment in observational studies will be allowed.
• Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent.
• Participants with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment.
• Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment with exceptions.
• Participants with confirmed human immunodeficiency virus (even if viral load is undetectable), chronic or active hepatitis B or C, or active hepatitis A.
• History of primary immunodeficiency, solid organ transplantation, or active tuberculosis (by clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
• Other invasive malignancy within 2 years. Non-invasive malignancies (i.e., cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured) are excluded from this definition.
• Known allergy or hypersensitivity to investigational product formulations.
• History of more than one event of infusion related reactions requiring permanent discontinuation of intravenous drug treatment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring antibiotic therapy, uncontrolled hypertension, bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events, or compromise the ability of the subject to give written informed consent.
• Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment with exceptions.
• Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment - Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Ipilimumab; CTLA-4 Antigen; Platinum Compounds

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Inorganic Chemicals

Study Officials

• Adrian Sacher, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: January 24, 2022
• Primary Completion: February 19, 2025
• Study Completion: February 19, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

CA (1)