Eligibility criteria
NSCLC, tumor, cancers, pembrolizumab, immune-mediated adverse reactions, respiratory or endocrine disorders, toxicity, malignancy, non-metastatic disease, neurologic or psychiatric disorder, hyperthyroidism, hypersensitivity, colitis, hepatic impairment, LCNEC, hypothyroidism, tumors, active infection
TUMOR, CANCERS, SIDE EFFECT, ADVERSE EVENTS, BRAIN METASTASES, DISEASE, DIABETES MELLITUS, HYPERTHYROIDISM, HYPERSENSITIVITY, NSCLC, CNS METASTASES, HYPOTHYROIDISM, TUMORS, METASTASES, AUTOIMMUNE DISEASE, IMMUNE-MEDIATED ADVERSE REACTION, LARGE CELL NEUROENDOCRINE CARCINOMA
Full eligibility criteria were as follows:Inclusion criteriaAdult patients (≥18 years of age) with previously untreated, histologically or cytologically confirmed metastatic PD-L1ECOG PS of 0 or 1.Patients have to be eligible to receive treatment with pembrolizumab as standard of care, have an ECOG PS of 0 or 1 and have measurable disease and acceptable organ function.No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Chemotherapy for non-metastatic disease (for example, adjuvant therapy) or immunotherapy for locally advanced stage III disease is allowed if at least 6 months have elapsed since the prior therapy and enrollment. Local therapy (for example, palliative extra-cranial radiation) is allowed as long as a period of 2 weeks has passed since completion. 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 28 d before patient enrollment and that wound healing has occurred.Clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST version 1.1.Imaging investigations, including computed tomography (CT) of the chest, abdomen and pelvis and magnetic resonance imaging (MRI) of the brain (if known brain metastases) or other scans as necessary to document all sites of disease must be done within 28 d before enrollment.Adequate hematology and organ function as defined below (must be done within 14 d before enrollment). Hematology: WBC ≥2.0 × 10Patients with large cell neuroendocrine carcinoma (LCNEC) and patients with clinically actionable Patients have to consent to provision of a representative archival formalin-fixed, paraffin-embedded (FFPE) tumor block.Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by a CLIA central laboratory and for correlative analysis by a research central laboratory.Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form before enrollment to the trial to document their willingness to participate.Patients must be accessible for treatment and follow-up. Investigators must assure themselves that 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 for any adverse events that may occur through the course of the trial.In accordance with CCTG policy, protocol treatment with pembrolizumab is to begin within two working days of patient enrollment.Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. A woman is considered to be of ‘childbearing potential’ if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, ‘effective contraception’ also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side effect of pregnancy prevention), defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the pre-study evaluation; this may include an ultrasound to rule out pregnancy if a false positive is suspected. For example, when beta-human chorionic gonadotropin is high and the partner is vasectomized, it may be associated with tumor production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy.Of note, a PD-L1 TPS ≥50% was initially indicated as an inclusion criterion for the BR.36 trial, given the regulatory approvals in the United States and in Canada at the time of study design and activation. Throughout the duration of the BR.36 trial, the practice guidance changed in both the United Stated and Canada, allowing for pembrolizumab monotherapy for NSCLC with PD-L1 TPS ≥1%, and this was reflected in a trial amendment and revision of the eligibility criteria to include NSCLC with PD-L1 TPS ≥1%. This amendment was implemented in January 2021, after which 18 patients were enrolled. Despite the revised eligibility criteria, most patients enrolled in BR.36 had tumors with PD-L1 ≥50%, reflecting the preference for pembrolizumab monotherapy in this context given the higher magnitude of benefit.Exclusion criteriaPatients with a prior malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.Patients with symptomatic central nervous system (CNS) metastases and/or CNS metastases requiring immunosuppressive doses of systemic corticosteroids (>10 mg per day prednisone equivalents). Patients with known CNS metastases who are asymptomatic and on a stable dose of corticosteroids ≤10 mg per day prednisone equivalents before enrollment are eligible.Patients who are not suitable candidates for treatment with pembrolizumab according to the current guidance/indications described in the Product Monograph (Canada) or Drug Label (US), 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 hypothyroidism or hyperthyroidism or diabetes mellitus), can be considered for enrollment to this study provided that pembrolizumab is administered with caution and patients are closely monitored.History of substantial 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.