Study of TBio-6517 Given Alone or in Combination With Pembrolizumab in Solid Tumors
- Conditions
- Cervical CancerSolid TumorMicrosatellite Stable Colorectal CancerCutaneous Squamous Cell CarcinomaMesotheliomaHPV Positive Oropharyngeal Squamous Cell CarcinomaRenal Cell CarcinomaOropharynx CancerMelanoma (Skin)
- Interventions
- Registration Number
- NCT04301011
- Lead Sponsor
- Turnstone Biologics, Corp.
- 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).
- 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 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. 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 27
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D: TBio-6517 intravenous and Pembrolizumab 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. TBio-6517 and Pembrolizumab in MSS-CRC Pembrolizumab 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. TBio-6517 and Pembrolizumab in HPV positive head and neck cancer TBio-6517 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. TBio-6517 and Pembrolizumab in HPV positive head and neck cancer Pembrolizumab 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. Arm D: TBio-6517 intravenous and Pembrolizumab TBio-6517 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. Arm A: TBio-6517 alone TBio-6517 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. TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin TBio-6517 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. Arm B: TBio-6517 and Pembrolizumab TBio-6517 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. Arm B: TBio-6517 and Pembrolizumab 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. TBio-6517 and Pembrolizumab in MSS-CRC TBio-6517 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. TBio-6517 and Pembrolizumab in cutaneous melanoma Pembrolizumab 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. TBio-6517 and Pembrolizumab in cutaneous melanoma TBio-6517 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. Arm C: TBio-6517 intravenous TBio-6517 Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months. TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin Pembrolizumab 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.
- Primary Outcome Measures
Name Time Method 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
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
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
- Secondary Outcome Measures
Name Time Method Time to tumor progression (TTP) 25 months Median time until patient disease progression (PD)
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
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)
Median progression free survival 25 months Median duration of progression free survival of patients
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
Trial Locations
- Locations (9)
The Billings Clinic
🇺🇸Billings, Montana, United States
National Cancer Center
🇰🇷Ilsandong, Korea, Republic of
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Sylvester Comprehensive Cancer Center / UMHC
🇺🇸Miami, Florida, United States
Clinical Site 1007
🇺🇸Boston, Massachusetts, United States
Seoul National University Hospital (SNUH)
🇰🇷Junggu, Korea, Republic of
Ottawa Hospital and Research Institute (OHRI)
🇨🇦Ottawa, Ontario, Canada
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States