A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT03206073
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • Durvalumab — DRUG
    1500 mg of durvalumab via intravenous (IV) infusion on Day 1 of each cycle until patients meet off treatment criteria
  • Tremelimumab — DRUG
    300 mg of tremelimumab via intravenous (IV) infusion on Day 1 of cycle 1
  • Pexa-Vec — BIOLOGICAL
    3 x 10E\^8 plaque-forming unit (pfu) (Dose Level (DL) 1) via intravenous (IV) infusion for 4 doses: Day 12, Day 2, Day 16 of Cycle 1 and Day 2 of Cycle 2.
  • Pexa-Vec — BIOLOGICAL
    1 x 10E\^9 pfu (DL 2) via intravenous (IV) infusion for 4 doses: Day 12, Day 2, Day 16 of Cycle 1 and Day 2 of Cycle 2.

Study Details

Background: * Immune-based approaches in colorectal cancer have unfortunately with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-hi) disease been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced disease colorectal cancer appears to be less immunogenic, as evidenced by the lack of infiltrating lymphocytes with advancing T stage * Pexa-Vec (JX-594) is a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte- macrophage colony-stimulating factor (GM-CSF) and beta-galactosidase. Apart from the direct oncolytic activity, oncolytic viruses such as Pexa-Vec have been shown to mediate tumor cell death via the induction of innate and adaptive immune responses * Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Durvalumab is a human monoclonal antibody directed against programmed death-ligand 1 (PD-L1). * The aim of the study is to evaluate whether the anti-tumor immunity induced by Pexa-Vec oncolytic viral therapy can be enhanced by immune checkpoint inhibition. Objective: -To determine the safety, tolerability and feasibility of Pexa-Vec oncolytic virus in combination with immune checkpoint inhibition in patients with refractory metastatic colorectal cancer. Eligibility: * Histologically confirmed metastatic colorectal cancer. * Patients must have progressed on, been intolerant of or refused prior oxaliplatin- and irinotecan-containing, fluorouracil-based, chemotherapeutic regimen and have disease that is not amenable to potentially curative resection. Patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type tumor must have progressed, been intolerant of or refused cetuximab or panitumumab based chemotherapy. * Patients tumors must be documented to be microsatellite-stable (MSS) either by genetic analysis or immunohistochemistry OR microsatellite-high with documented disease progression following anti-programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PDL1) therapy. * Patients must have at least one focus of metastatic disease that is amenable to pre- and on-treatment biopsy. * Willingness to undergo mandatory tumor biopsy. Design: -The proposed study is Phase I/II study of Pexa-Vec oncolytic virus at two dose levels in combination with immune checkpoint inhibition in patients with metastatic colorectal cancer.

Key Dates

Start date
Dec 7, 2017
Status verified
Sep 2023
Primary completion
Sep 24, 2020
Completion
Jun 30, 2022

Study Design

Enrollment
34 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: 1/Arm A1 Pexa-Vec + Durvalumab
    Pexa-Vec escalation dose levels + Durvalumab
  • Experimental: 2/Arm A2 Pexa-Vec +Durvalumab
    Maximum tolerated dose (MTD) of Pexa-Vec after the MTD is established +Durvalumab
  • Experimental: 3/Arm B1 Pexa-Vec + Durvalumab +Tremelimumab
    Pexa-Vec escalation dose levels + Durvalumab +Tremelimumab
  • Experimental: 4/Arm B2
    MTD of Pexa-Vec after the MTD is established+Durvalumab + Tremelimumab

Primary Outcome Measure

Number of Participants With Grade 1-5 Adverse Events [ Time Frame: 30 days after last treatment ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

Find similar trials in Bethesda, MD

By condition
Colorectal cancer
By specialty
OncologyGI oncology
By research site
National Institutes of Health Clinical Center· Bethesda, MD

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