Nivolumab With Ipilimumab Combined With TGFβ-15 Peptide Vaccine and Radiotherapy for Pancreatic Cancer

Sponsor
Inna Chen, MD
Study ID
NCT05721846
Phase
PHASE1
Status
Active Not Recruiting

Conditions

Eligibility Criteria

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

Interventions

  • Nivolumab — DRUG
    3 mg/kg (up to 240 mg maximum) as i.v. infusion on day 1 (± 3 days) of each 14-day treatment cycle
  • Ipilimumab — DRUG
    1 mg/kg as i.v. infusion on day 1 cycle 1 and subsequently every 6 weeks (± 3 days)
  • SBRT — RADIATION
    SBRT: 15 Gy x 1 on a single site of disease on day 1 cycle 1
  • TGFβ-B-15 peptide — BIOLOGICAL
    Vaccine (500 μl aqueous solution of 200 μg TGFβ-B-15 peptide mixed to an emulsion with 500μl Montanide ISA-51) as s.c. injection on day 1 of the first 6 cycles and subsequently every 4 weeks (± 3 days)

Study Details

"Non-immunogenicity" of PC with high prevalence of immunosuppressive cells and typically a scarcity of tumor-infiltrating effector lymphocytes is considered as one of the reasons for lacking responsiveness to single-agent immunotherapies. Considering the emerging role of the tumor microenvironment, the combination of checkpoint blocking antibodies with immunomodulation of the tumor microenvironment could lead to better responses in tumor historically resistant to radiation and checkpoint blocking antibody approaches as single modalities. For example, the data from the phase 2 study CheckPAC (NCT02866383) showed durable clinical benefit in a small subgroup of patients after adding SBRT of 15 Gy to a combination of nivolumab and ipilimumab (presented at ASCO GI 2022, San Fransisco) in patients with resistant metastatic PC. Furthermore, we have found that the TGFβ-15 immune response is corelated to clinical benefit, supporting the rationale for combining of TGFβ-15 peptide vaccine with CheckPAC strategy (SBRT of 15 in combination with nivolumab and ipilimumab).

Key Dates

Start date
May 3, 2023
Status verified
Sep 2025
Primary completion
May 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
20 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental
    SBRT: 15 Gy x 1 on a single site of disease on day 1 cycle 1 Immunotherapy: Nivolumab 3 mg/kg (up to 240 mg maximum) as i.v. infusion on day 1 (± 3 days) of each 14-day treatment cycle Ipilimumab 1 mg/kg as i.v. infusion on day 1 cycle 1 and subsequently every 6 weeks (± 3 days). Vaccine (500 μl aqueous solution of 200 μg TGFβ-B-15 peptide mixed to an emulsion with 500μl Montanide ISA-51) as s.c. injection on day 1 of the first 6 cycles and subsequently every 4 weeks (± 3 days)

Primary Outcome Measure

Adverse events [ Time Frame: 6 months ]

Related Studies