Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy

Sponsor
Joachim Aerts, MD PhD
Study ID
NCT05927142
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Metastatic Pancreatic Cancer

Eligibility Criteria

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

Interventions

  • Durvalumab — BIOLOGICAL
    Human anti-PD-L1 antibody
  • Rintatolimod — DRUG
    TLR-3 agonist, synthetic double-stranded ribonucleic acid (poly I:C12U)

Study Details

Pancreatic ductal adenocarcinoma (PDAC) is estimated to become the second leading cause of cancer-related death by 2030. Effective management of PDAC is challenged by a combination of late diagnosis, lack of effective screening methods and high risk of early metastasis. Although systemic chemotherapy improves survival, 5-year survival is only 6%. Chemotherapy efficacy is attenuated by innate and acquired drug resistance of tumor cells, a strong desmoplastic reaction that limits local accessibility of drugs and a "cold" tumor microenvironment (TME) with high infiltrating levels of immunosuppressive cells. In PDAC, increased T cell exhaustion defined by increased PD-1/PD-L1 activity in both peripheral blood and tumor microenvironment, is associated with poor prognosis. Hence the rationale for targeting the PD-1/PD-L1 axis with the aim to release the "brake" and exert an anti-tumor response. In PDAC successful results with Immune Checkpoint Inhibition (ICI) monotherapy are limited and combination therapy with other agents is encouraged; specifically agents that induce dendritic cell priming. We hypothesize that combination therapy of ICI therapy with a toll like receptor 3 (TLR-3) agonist is a potential effective strategy. TLR-3 agonists are hypothesized to increase dendritic cell maturation and cross-priming naïve cytotoxic CD8 T cells while eliminating regulatory T-cell attraction, thereby acting as an immune-boosting agent. We propose that rintatolimod/durvalumab-combination therapy is feasible and may induce synergistic anti-tumor immune responses in PDAC.

Key Dates

Start date
Jan 9, 2024
Status verified
Feb 2025
Primary completion
Apr 30, 2026
Completion
Apr 30, 2027

Study Design

Enrollment
43 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER

Arms

  • Experimental: Durvalumab and rintatolimod combination therapy
    1500mg Durvalumab administered via IV infusion once every first day of a 28 day cycle for a total of maximum 12 cycles (12 infusions in total). 200-400mg Rintatolimod administered via IV infusion twice per week for a total of 6 weeks (12 infusions in total).

Primary Outcome Measure

Phase Ib: Determine safety of combination therapy with durvalumab and rintatolimod [ Time Frame: from the start of rintatolimod until 6 weeks after the first day of the first cycle of durvalumab (one cycle is 28 days) ]

Central Contacts

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