Study of Nivolumab-Ipilimumab and cfDNA in Lung Cancer

Inclusion Criteria:

• Age ≥ 18 years at the time of screening or age of consent.

• Written informed consent obtained from the subject prior to performing anyprotocol-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, regardlessof prior treatment with tyrosine kinase inhibitors

• No prior radiation, surgery or chemotherapy is allowed for the current diagnosis ofnon-small cell lung cancer

• Adequate organ and marrow function

Exclusion Criteria:

• Receipt of any conventional or investigational anticancer therapy within 21 days orpalliative radiotherapy within 14 days prior to the scheduled first dose of studytreatment.

• Prior receipt of any immune-mediated therapy.

• Incomplete surgical resection

• Concurrent enrolment in another therapeutic clinical study. Enrolment inobservational studies will be allowed.

• Any toxicity (excluding alopecia) from prior standard therapy that has not beencompletely 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 FunctionalClassification or stroke within the past 3 months prior to the scheduled first doseof study treatment.

• Active or prior documented autoimmune disorders within the past 3 years prior to thescheduled first dose of study treatment with exceptions.

• Participants with confirmed human immunodeficiency virus (even if viral load isundetectable), chronic or active hepatitis B or C, or active hepatitis A.

• History of primary immunodeficiency, solid organ transplantation, or activetuberculosis (by clinical evaluation that includes clinical history, physicalexamination and radiographic findings, and tuberculosis testing in line with localpractice).

• Other invasive malignancy within 2 years. Non-invasive malignancies (i.e., cervicalcarcinoma 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 excludedfrom this definition.

• Known allergy or hypersensitivity to investigational product formulations.

• History of more than one event of infusion related reactions requiring permanentdiscontinuation of intravenous drug treatment.

• Uncontrolled intercurrent illness including, but not limited to ongoing or activeinfection requiring antibiotic therapy, uncontrolled hypertension, bleedingdiatheses, or psychiatric illness/social situations that would limit compliance withstudy requirements, substantially increase risk of incurring adverse events, orcompromise the ability of the subject to give written informed consent.

• Current or prior use of immunosuppressive medication within 14 days prior to thescheduled first dose of study treatment with exceptions.

• Receipt of live, attenuated vaccine within 30 days prior to the scheduled first doseof study treatment - Major surgery within 28 days prior to scheduled first dose ofstudy treatment or still recovering from prior surgery.

• Females who are pregnant, lactating, or intend to become pregnant during theirparticipation in the study.

• Participants who are involuntarily incarcerated or are unable to willingly provideconsent or are unable to comply with the protocol procedures.

• Any condition that, in the opinion of the investigator, would interfere with safeadministration or evaluation of the investigational products or interpretation ofsubject safety or study results.