Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors
NCT05269381 · Phase 1, Phase 2 · Jacksonville, Florida, United States
- Condition
- Sarcoma
- Disease stage
- Stage I-IV
- Phase
- Phase 1, Phase 2
- Study type
- DRUG, BIOLOGICAL, PROCEDURE
- Intervention
- Cyclophosphamide
- Age
- 16 Years to
- Gender
- All
- Sponsor
- Mayo Clinic
- Research institution
- Mayo Clinic
- Facility
- Mayo Clinic in Florida
- Research center
- Mayo Clinic in Florida
Summary
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Detailed description
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.
Inclusion criteria
Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling. PHASE I PRE-REGISTRATION, ALL: * Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests * NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration. * NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed. * Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease * Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy * Provide written informed consent. For pediatric patients (age 16-17 years): * Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations. * Willing to return to enrolling institution for follow-up * Willing to provide blood specimens for research * Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential. * Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle * Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 * Anticipated life expectancy \> 6 months * Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo). * The following lab values obtained ≤ 28 days prior to pre-registration: * Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion) * Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L * Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion) * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases * Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy PHASE I REGISTRATION, ALL: * Successful sequencing and production of REAL-Neo vaccine * Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease * ECOG PS 0 or 1 * Anticipated life expectancy \> 6 months * The following lab values obtained ≤ 14 days prior to registration: * Hemoglobin ≥ 9.0 g/dl * ANC ≥ 1500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 1.5 x ULN * ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement) * PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy * Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula * Provide written informed consent * Willing to provide blood and tissue sp
Primary outcomes
Maximally tolerated dose (MTD) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5); Dose Limiting Toxicity (DLT) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5); Incidence of adverse events (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)
Secondary outcomes
Immunogenicity response rate (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5); Incidence of adverse events (Phase II); Immunogenicity response rate (Phase II)