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

NCT ID: NCT04301011

Last Updated: 2025-04-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-02
• Study Completion Date: 2023-01-23

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.

Conditions

Solid Tumor; Microsatellite Stable Colorectal Cancer; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Cervical Cancer; Melanoma (Skin); Cutaneous Squamous Cell Carcinoma; Mesothelioma; Renal Cell Carcinoma; Oropharynx Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

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.

Group Type: EXPERIMENTAL

TBio-6517

Intervention Type: BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Pembrolizumab

Intervention Type: BIOLOGICAL

Immune checkpoint inhibitor.

Interventions

TBio-6517

Engineered Oncolytic Vaccinia Virus

Intervention Type: BIOLOGICAL

Pembrolizumab

Immune checkpoint inhibitor.

Intervention Type: BIOLOGICAL

Other Intervention Names

RIVAL-01; Keytruda

Eligibility Criteria

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

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. 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)

2. 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

3. Locally advanced or metastatic cSCC (Cohort 3) that has not received systemic therapy (e.g., local resection or local topical therapy is permitted).

4. 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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Turnstone Biologics, Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ines Verdon, MD

Role: STUDY_DIRECTOR

Turnstone Biologics

Locations

Mayo Clinic

Phoenix, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

Sylvester Comprehensive Cancer Center / UMHC

Miami, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Clinical Site 1007

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

The Billings Clinic

Billings, Montana, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Ottawa Hospital and Research Institute (OHRI)

Ottawa, Ontario, Canada

National Cancer Center

Ilsandong, , South Korea

Seoul National University Hospital (SNUH)

Junggu, , South Korea

Countries

United States; Canada; South Korea

Other Identifiers

TBio-6517-ITu-001

Identifier Type: -

Identifier Source: org_study_id