Clinical Trials /

Study of TBio-6517, Given Intratumorally, Alone or in Combination With Pembrolizumab, in Solid Tumors

NCT04301011

Description:

To determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) alone and when combined with pembrolizumab in patients with solid tumors (RIVAL-01).

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of TBio-6517, Given Intratumorally, Alone or in Combination With Pembrolizumab, in Solid Tumors
  • Official Title: A Phase 1/2a, Multicenter, Open-label Trial of TBio-6517, an Oncolytic Vaccinia Virus, Administered by Intratumoral Injection, Alone and in Combination With Pembrolizumab, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TBio-6517-ITu-001
  • NCT ID: NCT04301011

Conditions

  • Solid Tumor
  • Triple Negative Breast Cancer
  • Microsatellite Stable Colorectal Cancer

Interventions

DrugSynonymsArms
TBio-6517RIVAL-01Arm A: TBio-6517 alone
PembrolizumabKeytrudaArm B: TBio-6517 and Pembrolizumab

Purpose

To determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) alone and when combined with pembrolizumab in patients with solid tumors (RIVAL-01).

Detailed Description

      This is a Phase 1/2a dose escalation study with TBio-6517 administered by direct injection
      into tumor(s). The Phase 1 portion has 2 arms; the first arm (Arm A) will determine the RP2D
      of TBio-6517 alone when directly injected into tumor(s), and the second arm (Arm B) will
      determine the RP2D of TBio-6517 when combined with pembrolizumab.

      In the Phase 2a portion, the clinical benefit of TBio-6517 combined with pembrolizumab will
      be further explored in patients with Triple Negative Breast Cancer (TNBC) or Microsatellite
      Stable Colorectal Cancer (MSS-CRC) as assessed by overall response rate (ORR) from central
      radiology review.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: TBio-6517 aloneExperimentalDose escalation of TBio-6517 alone administered by direct injection into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months.
  • TBio-6517
Arm B: TBio-6517 and PembrolizumabExperimentalDose escalation of TBio-6517 administered in combination with pembrolizumab. TBio-6517 will be directly injected into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months. Pembrolizumab will be administered beginning at Day 8 via intravenous (IV) infusion every 3 weeks for up to 24 months.
  • TBio-6517
  • Pembrolizumab
TBio-6517 and Pembrolizumab in MSS-CRCExperimentalDoses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 8 given every 3 weeks for up to 24 months in patients with microsatellite stable colorectal carcinoma (MSS-CRC). Booster injections of TBio-6517 are permitted for up to 24 months.
  • TBio-6517
  • Pembrolizumab
TBio-6517 and Pembrolizumab in TNBCExperimentalDoses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 8 given every 3 weeks for up to 24 months in patients with triple negative breast cancer (TNBC). Booster injections of TBio-6517 are permitted for up to 24 months.
  • TBio-6517
  • Pembrolizumab

Eligibility Criteria

        Key Inclusion Criteria:

          -  Have a histologically or pathologically documented, locally-advanced or metastatic
             solid tumor for which standard curative measures do not exist or are no longer
             effective

          -  Measurable disease as per RECIST 1.1 criteria

          -  At least one tumor amenable to safe ITu injections and biopsies

          -  ECOG performance status 0 or 1

          -  Demonstrate adequate organ function

          -  Must be willing to comply with all protocol procedures and adhere to post-treatment
             care instructions

          -  Additional Inclusion criteria exist

        For patients in phase 2 only: Have a histologically or cytologically confirmed advanced
        (metastatic and/or unresectable) solid tumor listed below, that is incurable and for which
        prior standard treatment has failed:

          1. MSS-CRC patients that have progressed to at least 2 prior lines of systemic therapy
             which should include irinotecan and oxaliplatin with or without bevacizumab, or,

          2. TNBC patients who have failed anthracycline- and taxane-based chemotherapy. TNBC
             patients with PD-L1 positive tumors must also have failed treatment with PD-1 or PD-L1
             targeted therapy.

        Key Exclusion Criteria:

          -  Prior systemic therapy, including experimental, surgery or radiation therapy within 4
             weeks and must have recovered from acute toxicity.

          -  Prior treatment with any oncolytic virus.

          -  Requires use of anti-platelet or anti-coagulant therapy that cannot be safely
             suspended for per protocol biopsies or intra-tumoral injections.

          -  CNS metastases and/or carcinomatous meningitis that have not been completely resected
             or completely irradiated.

          -  Prior history of myocarditis

          -  Symptomatic or asymptomatic cardiovascular disease

          -  Known HIV/AIDS, active HBV or HCV infection.

          -  Received immunosuppressive medication within 4 weeks. (>10mg/day prednisone)

          -  Known intolerance to anti-PD-1 or anti-PD-L1 antibody therapy

          -  Additional Exclusion criteria exist
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level
Time Frame:25 months
Safety Issue:
Description:Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0

Secondary Outcome Measures

Measure:Number and severity of adverse events at the RP2D
Time Frame:25 months
Safety Issue:
Description:Number of patients with adverse events by severity and frequency as determined by NCI CTCAE v5.0
Measure:Median overall survival (OS)
Time Frame:48 months
Safety Issue:
Description:Median overall survival in months in patients
Measure:Median Duration of Response (DoR)
Time Frame:25 months
Safety Issue:
Description:Median duration of response in patients with a CR or PR
Measure:Proportion of patients with a response (ORR)
Time Frame:25 months
Safety Issue:
Description:Percentage of patients in all arms with a CR or PR as assessed by the central radiologist using RECIST 1.1 and iRECIST
Measure:Median Disease Control Rate (DCR)
Time Frame:25 months
Safety Issue:
Description:Median duration of response in patients with a CR, PR, or stable disease (SD)
Measure:Time to tumor progression (TTP)
Time Frame:25 months
Safety Issue:
Description:Median time until patient disease progression (PD)
Measure:Median progression free survival
Time Frame:25 months
Safety Issue:
Description:Median duration of progression free survival of patients

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Turnstone Biologics, Corp.

Trial Keywords

  • TNBC
  • CRC
  • MSS-CRC
  • Oncolytic Virus
  • Intratumoral injection

Last Updated

March 6, 2020