PolyImmune {Durvalumab (MEDI4736) and Tremelimumab} & Vaccine Orchestrated Treatment for Patients With Advanced/Metastatic Renal Cell Carcinoma

Sponsor
Washington University School of Medicine
Study ID
NCT03598816
Phase
PHASE2
Status
Withdrawn

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    -Durvalumab infusion will start approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion
  • Tremelimumab — DRUG
    -Tremelimumab will be administered first
  • TDS-IM v1.0 System — DEVICE
    -Integrated electroporation device
  • Neoantigen DNA Vaccine — BIOLOGICAL
    -At each vaccination time point, patients will receive two injections of the neoantigen DNA vaccine, one injection into each deltoid or lateralis.
  • Research blood draw — PROCEDURE
    -Baseline, C2D1, C3D1, C5D1, C7D1, and C9D1

Study Details

Reported in the 2018 NEJM (378; 1277) article, the combination of checkpoint inhibitors ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) phase III trial Checkmate 214 demonstrated statistically significant (P\<0.0001) improvement of overall response rate (ORR) at 42% (95% confidence interval (CI), 37-47%) compared to standard of care (SOC) sunitinib at 27% (95% CI, 22-31%) in treatment naïve advanced or metastatic clear cell renal cell carcinoma (ccRCC). This study also showed increased survival benefit of Ipi+Nivo over sunitinib in the IMDC intermediate-poor risk ccRCC patients. Accordingly, the Ipi+Nivo was just approved by U.S. FDA in April 2018 for treating metastatic ccRCC. Hence, the investigators hypothesized that the combination of durvalumab and tremelimumab is similarly efficacious in advanced or metastatic RCC. Furthermore, the investigators also hypothesize that the administration of personalized neoantigen DNA vaccine will further enhance anti-tumor immune response in RCC.

Key Dates

Start date
Aug 31, 2020
Status verified
Aug 2020
Primary completion
Dec 31, 2022
Completion
May 31, 2024

Study Design

Enrollment
0 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1: Durvalumab + Tremelimumab + Neoantigen DNA Vaccine
    * All patients will receive durvalumab intravenous (IV) at a dose of 10 mg/kg over the course of 60 minutes given every 2 weeks (on Days 1 and 15 of each 28-day cycle) for a total of 8 doses. Durvalumab will be given thereafter as monotherapy at a dose of 209 mg/kg over the course of 60 minutes given every 4 weeks (on Day 1 of each 28-day cycle) for a total of 4 doses * All patients will receive tremelimumab at a dose of 1 mg/kg over the course of 60 minutes given every 4 weeks (on Day 1 of each 28-day cycle) for a total of 4 cycles * The first vaccination will take place two weeks after confirmed disease progression on targeted therapy. This will be Day 1 of the first 28-day cycle of treatment with durvalumab and tremelimumab * The schedule of vaccination is Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, and Cycle 5 Day 1 (for a total of 6 doses)
  • Experimental: Arm 2: Durvalumab + Tremelimumab
    * All patients will receive durvalumab IV at a dose of 10 mg/kg over the course of 60 minutes given every 2 weeks (on Days 1 and 15 of each 28-day cycle) for a total of 8 doses. Durvalumab will be given thereafter as monotherapy at a dose of 209 mg/kg over the course of 60 minutes given every 4 weeks (on Day 1 of each 28-day cycle) for a total of 4 doses * All patients will receive tremelimumab at a dose of 1 mg/kg over the course of 60 minutes given every 4 weeks (on Day 1 of each 28-day cycle) for a total of 4 cycles.

Primary Outcome Measure

Safety of the combination of durvalumab & tremelimumab with or without neoantigen DNA vaccine when given to patients with renal cell carcinoma as measured by the percentage of patients with adverse events of grade 3 or higher [ Time Frame: Completion of cycle 1 (4 weeks) ]

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