A Phase II Study of the Effects of Pembrolizumab on Quality of Life for Patients With Treatment-Naïve, Advanced or Metastatic NSCLC and Poor Performance Status
This single center open-label trial will enroll a single cohort of patients with advanced non-small cell lung cancer (NSCLC) who are ineligible for treatment with curative intent due to 1) disease stage IV, or 2) inability to tolerate intensive surgery or chemo-radiation. Patients will be eligible for the trial if ISMMS reviewed samples from tumor biopsy have a PDL-1 TPS ≥ 1% and have ECOG performance status rated 2 or 3. All patients will receive anti PD-1 therapy with pembrolizumab 200mg IV every 3 weeks, during which patients will also undergo serial QOL assessments. This trial will follow a phase II single arm, open label design. The study will enroll 45 patients evaluable for the primary endpoint of which will be change in QOL as measured by the EORTC's QLQ-C30 between Day 1 and Day 84 +/- 7 days. Secondary outcomes including evaluation for development of confounding mental health conditions will be evaluated via serial HADS assessments. Concomitant radiographic assessment with PET/CT, regardless of the doses of pembrolizumab received, will allow for evaluation of secondary efficacy outcomes, including disease response by RECIST 1.1 criteria.
• Men and women, aged 18 years and older, with locally advanced NSCLC who are ineligible for definitive surgical resection or concurrent chemoradiation, or metastatic NSCLC
• Patients must not have received any systemic therapy for metastatic cancer
• Patients must not have received any PD-1 or PD-L1 inhibitor
• ECOG performance status of 2 or 3 at the time of consent and on the first day of therapy
• Patients may not have a molecular alteration in ALK, ROS1, EGFR, BRAF, NTRK, RET, MET, or any other gene for which first-line FDA approved targeted therapy exists.
• Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS directed therapy is not required and is unlikely to be required during the first cycle of therapy.
• Patients with HIV on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this trial.
• Adequate organ and marrow function as defined below:
‣ Leukocytes ≥ 3,000/mcL
⁃ Absolute neutrophil count ≥ 1,000/mcL
⁃ Platelets ≥ 100,000/mcl
⁃ Total bilirubin ≤ 1.5 x ULN
⁃ AST (SGOT)/ALT (SPGT) ≤ 3 x ULN or ≤5 x ULN if liver metastases present
⁃ GFR (Cockroft-Gault) ≥ 30 mL/min
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 3 days prior to C1D1 of pembrolizumab therapy. For the purposes of this trial, WOCBP are defined as women who have had a menstrual period within the last 48 months.
• Provision of signed and dated informed consent form
• Ability to take the study medication, and complete the study questionnaires
• Stated willingness to comply with all study procedures for the duration of the study
• For women of reproductive potential, agreement to use highly effective contraception during study treatment and for at least 4 months after the final dose
• For men of reproductive potential, agreement to use condoms or other methods to ensure effective contraception with female partners of reproductive potential