Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors

PRIMARY OBJECTIVE: I. To evaluate the safety of personalized neoantigen peptide vaccine in combination with pembrolizumab in advanced solid cancers. (Phase I and Pilot Cohort 5) II. To evaluate and estimate 24-months event-free survival (EFS) rate per Kaplan-Meier method in triple-negative breast cancer (TNBC) patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) III. To evaluate and estimate 24-months event-free survival (DFS) rate per Kaplan-Meier method in stage II/III non-small cell lung cancer (NSCLC) patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) SECONDARY OBJECTIVES: I. To evaluate and estimate the immunogenicity response rate in patients with advanced solid cancers receiving personalized neoantigen peptide vaccine in combination with pembrolizumab. (Phase I and Pilot Cohort 5) II. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response. III. To evaluate and estimate the immunogenicity response rate in TNBC patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) IV. To evaluate adverse event profile in in TNBC patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) V. To evaluate and estimate the vaccine immunogenicity response rate in stage II/III NSCLC patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) VI. To evaluate adverse event profile in stage II/III NSCLC patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) EXPLORATORY OBJECTIVES: I. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response in patients with selected advanced solid tumors. (Phase I and Pilot Cohort 5) II. To obtain preliminary estimates of efficacy as measured by objective response rate (ORR based on Response Evaluation Criteria in Solid Tumors \[RECIST\]) of personalized neoantigen peptide vaccine and pembrolizumab in patients with selected advanced solid tumors. (Phase I and Pilot Cohort 5) III. To obtain preliminary information of immunity persistence, as well as pre-existing immunity in patients with selected advanced solid tumors. (Phase I and Pilot Cohort 5) IV. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response in Cohort 1 (TNBC patients with RCB-2 and RCB-3) and 2 (stage II/III NSCLC patients) separately. (Phase II) V. To obtain preliminary information of immunity persistence, as well as pre-existing immunity in Cohort 1 (TNBC patients with RCB-2 and RCB-3) and 2 (stage II/III NSCLC patients) separately. (Phase II) OUTLINE: This is a phase I, dose-escalation study of personalized neoantigen vaccine followed by a phase II study. Patients are assigned to 1 of 5 cohorts. COHORT 1: Patients receive cyclophosphamide intravenously (IV) on day -3. Patients then receive personalized neoantigen vaccine with sargramostim (GM-CSF) subcutaneously (SC) on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. COHORT 2: Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT 3: Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT 4: Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. PILOT COHORT 5: Patients with ILC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembroblizumab IV on day of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 3 months up to 2 years from study enrollment.