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

Maximally tolerated dose (MTD) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)

MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. For instance, those toxicities with an incidence of at least 25% will be observed with a probability of at least 82% (1-(1-0.25).

Dose Limiting Toxicity (DLT) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)

DLT are defined to be adverse event (AE) occurring from day -3 through day 35 that is possibly, probably, or definitely related to neoantigen peptide vaccine with/without pembrolizumab and fulfills any of the following criteria using the National Cancer Institute's Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0

Incidence of adverse events (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)

The number and severity (grade) of all treatment related adverse events (AEs) will be tabulated and summarized. Non-hematologic AEs will be evaluated via the ordinal CTCAE v5.0 standard AE grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTCAE v5.0 standard AE grading. Both all grade and grade 3 and above AEs will be described and summarized in a similar fashion. Overall AE incidences as well as AE profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

Event free survival (EFS) (Phase II Cohort 3)

EFS is defined as the length of time after primary treatment for a cancer ends until occurrence of complications or events that the treatment was intended to prevent or delay.

Immunogenicity response rate (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)

Will be defined as number of patients who have ≥ 20% of neoantigens formulated into vaccine with at least 3-folds of value increase at any timepoint within 24 weeks, divided by total number of evaluable patients. Evaluable patients are defined as patients who are properly registered and received at least one dose of vaccine.

Incidence of adverse events (Phase II)

Will be assessed using CTCAE v5.0. Defined as the proportion of patients experienced at least one grade 3, grade 4, or grade 5 of each type of AE during the protocol defined treatment. The binary endpoints will be estimated, in each cohort (or by dose level. Dose intensity and number of cycles will be summarized by mean, standard deviation, median, Q1, Q3, and range, in each cohort. The maximum grade for each type of adverse events that are possibly, probably, or definitely related to study treatments will be recorded for each patient. The frequency tables will be reviewed to determine the patterns.

Immunogenicity response rate (Phase II)

Will be defined as number of patients who have ≥ 20% of neoantigens formulated into vaccine with at least 3-folds of value increase at any timepoint within 24 weeks, divided by total number of evaluable patients. Evaluable patients are defined as patients who are properly registered and received at least one dose of vaccine.

Objective response rate (Phase I and Pilot Cohort 5)

Will be defined as number of patients who achieve complete response or partial response per Response Evaluation Criteria in Solid Tumors criteria version 1.1, confirmed based on at least two consecutive evaluations with 6 weeks apart or at the next re-staging computed tomography scan determined by treating physician, divided by total number of evaluable patients.

Persistence Immunogenicity response rate (Phase I and Phase II)

Will be defined as number of patients who have as at least 3-folds of value increase of any neoantigen from baseline at 12 months among neoantigens that had been detected with at least 3-folds of value increase within 24 weeks from baseline, divided by total number of evaluable patients.

Pre-existing Immunity (Phase I and Phase II)

Will be defined as number of patients with mean antigen-specific T cell frequency is statistically higher (P\<0.05) from no antigen wells at baseline, divided by total number of evaluable patients.