RAPTOR: Study of TBio-6517 Given Alone or in Combination With Pembrolizumab in Solid Tumors
Study Details
Study Description
Brief Summary
To determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) or intravenously and when combined with pembrolizumab in patients with solid tumors (RIVAL-01).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a Phase 1/2a dose escalation study with TBio-6517 administered by direct injection into tumor(s) or by intravenous infusion. The Phase 1 portion has 4 arms; the first arm (Arm
- 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. The third and fourth arms will determine the RP2D of TBio-6517 when given intravenously alone and with pembrolizumab, respectively.
In the Phase 2a portion, the clinical benefit of TBio-6517 combined with pembrolizumab will be further explored in patients with Microsatellite Stable Colorectal Cancer (MSS-CRC), Cholangiocarcinoma (CCA), Cutaneous Melanoma, and Cutaneous Squamous Cell Carcinoma of the Skin (cSCC), as assessed by overall response rate (ORR) from central radiology review.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A: TBio-6517 alone 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. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
|
Experimental: Arm B: TBio-6517 and Pembrolizumab 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 9 via intravenous (IV) infusion every 3 weeks for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Experimental: TBio-6517 and Pembrolizumab in MSS-CRC Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 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. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Experimental: TBio-6517 and Pembrolizumab in cutaneous melanoma Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 given every 3 weeks for up to 24 months in patients with malignant melanoma of the skin. Booster injections of TBio-6517 are permitted for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Experimental: TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin 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 cSCC. Booster injections of TBio-6517 are permitted for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Experimental: TBio-6517 and Pembrolizumab in HPV positive head and neck cancer Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 given every 3 weeks for up to 24 months in patients with HPV associated oropharyngeal cancer. Booster injections of TBio-6517 are permitted for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Experimental: Arm C: TBio-6517 intravenous Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
|
Experimental: Arm D: TBio-6517 intravenous and Pembrolizumab Dose escalation of TBio-6517 administered in combination with pembrolizumab. Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months. Pembrolizumab will be administered beginning at Day 9 via intravenous (IV) infusion every 3 weeks for up to 24 months. |
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Names:
Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level [25 months]
Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0
- Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) when combined with pembrolizumab [25 months]
Percentage of patients with adverse events by severity as determined by NCI CTCAE v5.0
- Maximum tolerated dose (MTD) or Maximum feasible dose (MFD) and determination of the recommended Phase 2 dose (RP2D) of TBio-6517 alone and in combination with pembrolizumab. [4 weeks]
The highest dose of TBio-6517 that can be administered where fewer than 2 patients have a dose-limiting safety event alone or when combined with pembrolizumab as assessed by NCI CTCAE v.5.0 during the Phase 1 dose escalation
- Percentage of overall response rate (ORR) by RECIST 1.1 at the RP2D [25 months]
Percentage of patients treated at the RP2D in combination with pembrolizumab with a partial response or complete response by RECIST 1.1 following central radiologist review
- Percentage of overall response rate (ORR) by immunotherapy RECIST (iRECIST) at the RP2D [25 months]
Percentage of patients treated at the RP2D with pembrolizumab with a partial response (PR) or complete response (CR) by iRECIST following central radiologist review
Secondary Outcome Measures
- Number and severity of adverse events at the RP2D [25 months]
Number of patients with adverse events by severity and frequency as determined by NCI CTCAE v5.0
- Median overall survival (OS) [48 months]
Median overall survival in months in patients
- Median Duration of Response (DoR) [25 months]
Median duration of response in patients with a CR or PR
- Proportion of patients with a response (ORR) [25 months]
Percentage of patients in all arms with a CR or PR as assessed by the central radiologist using RECIST 1.1 and iRECIST
- Median Disease Control Rate (DCR) [25 months]
Median duration of response in patients with a CR, PR, or stable disease (SD)
- Time to tumor progression (TTP) [25 months]
Median time until patient disease progression (PD)
- Median progression free survival [25 months]
Median duration of progression free survival of patients
Eligibility Criteria
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:
-
Advanced (unresectable) or metastatic, intra or extra hepatic adenocarcinoma originating from the bile duct, CCA (Cohort 1) having progressed on at least 1 line of systemic therapy (including targeted therapy if eligible)
-
Locally advanced or metastatic cutaneous melanoma (Cohort 2) that has failed anti-PD-1 or anti-PDL1 therapy (+/- anti-CTLA-4 therapy) and if BRAF+, having failed a BRAF/ +/-MEK inhibitor
-
Locally advanced or metastatic cSCC (Cohort 3) that has not received systemic therapy (e.g., local resection or local topical therapy is permitted).
-
Locally advanced or metastatic MSS-CRC (Cohort 4) patients that have progressed on at least 2 prior lines of systemic therapy which should include irinotecan and oxaliplatin +/- targeted therapy if warranted.
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mayo Clinic | Phoenix | Arizona | United States | 85054 |
2 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
3 | Sylvester Comprehensive Cancer Center / UMHC | Miami | Florida | United States | 33136 |
4 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66205 |
5 | Clinical Site 1007 | Boston | Massachusetts | United States | 02215 |
6 | Mayo Clinic | Rochester | Minnesota | United States | 55902 |
7 | The Billings Clinic | Billings | Montana | United States | 31031 |
8 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
9 | Ottawa Hospital and Research Institute (OHRI) | Ottawa | Ontario | Canada | |
10 | National Cancer Center | Ilsandong | Korea, Republic of | 10408 | |
11 | Seoul National University Hospital (SNUH) | Junggu | Korea, Republic of | 03080 |
Sponsors and Collaborators
- Turnstone Biologics, Corp.
- Takeda
Investigators
- Study Director: Justine Walker, MD, Turnstone Biologics, Corp.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TBio-6517-ITu-001