The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
1. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and on Day 1 of cycle 2, 3 and 4 (priming phase). Boost vaccinations: every 3 cycles beginning C5D1. 2. Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5mg Poly-ICLC
1. Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 1-4 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 5. 2. Drug: 3mg/kg and 480mg IV
1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 1, 2, 3 and 4 of the study, every 3 weeks of the priming phase. 2. Drug: 1mg/kg IV
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
RECRUITINGAll Cohorts: Number of participants experiencing study drug-related toxicities
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Time frame: 4 years
All Cohorts: Fold change in interferon-producing DNAJB1-PRKACA-specific CD4 and CD8 T cells at 10 weeks
Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD8 cells after vaccination at 10 weeks compare to pre-vaccination baseline.
Time frame: Baseline and 10 weeks
Cohort A only: Progression-free survival (PFS)
PFS at 6 months, will be estimated as the proportion of subjects who remain alive and free of disease progression at 6 months from the start of treatment. Disease progression will be determined using RECIST 1.1 criteria. The proportion of subjects achieving PFS at 6 months will be estimated using the Kaplan-Meier method, and the corresponding 95% confidence interval will be reported.
Time frame: 6 months
Objective response rate (ORR)
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: 4 years
Duration of response (DoR)
Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date of disease progression or death is documented per RECIST 1.1. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.
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Time frame: 4 years
Disease control rate (DCR)
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: 4 years
Progression-free survival (PFS)
PFS is defined as number of months from the date of first treatment until first documented local progression or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time frame: 4 years
Overall survival (OS)
OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Time frame: 4 years