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).
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
Drug | Synonyms | Arms |
---|
TBio-6517 | RIVAL-01 | Arm A: TBio-6517 alone |
Pembrolizumab | Keytruda | Arm 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
Name | Type | Description | Interventions |
---|
Arm A: TBio-6517 alone | Experimental | Dose 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. | |
Arm B: TBio-6517 and Pembrolizumab | Experimental | Dose 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 and Pembrolizumab in MSS-CRC | Experimental | Doses 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 and Pembrolizumab in TNBC | Experimental | Doses 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. | |
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: | Recruiting |
Lead Sponsor: | Turnstone Biologics, Corp. |
Trial Keywords
- TNBC
- CRC
- MSS-CRC
- Oncolytic Virus
- Intratumoral injection
Last Updated
May 7, 2021