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

Cervical Cancer Clinical Trial

— RAPTOR  

Official title:

A Phase 1/2a, Multicenter, Open-label Trial of TBio-6517, an Oncolytic Vaccinia Virus, Administered Alone and in Combination With Pembrolizumab, in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04301011
• Other study ID #: TBio-6517-ITu-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 2, 2020
• Est. completion date: January 23, 2023

Study information

• Verified date: November 2023
• Source: Turnstone Biologics, Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: January 23, 2023
• Est. primary completion date: January 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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.

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Cervical Cancer
• Cutaneous Squamous Cell Carcinoma
• HPV Positive Oropharyngeal Squamous Cell Carcinoma
• Melanoma
• Melanoma (Skin)
• Mesothelioma
• Mesothelioma, Malignant
• Microsatellite Stable Colorectal Cancer
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Renal Cell Carcinoma
• Solid Tumor
• Squamous Cell Carcinoma of Head and Neck
• Uterine Cervical Neoplasms

Intervention

Biological:
• TBio-6517
Engineered Oncolytic Vaccinia Virus
• Pembrolizumab
Immune checkpoint inhibitor.

Locations

Country	Name	City	State
Canada	Ottawa Hospital and Research Institute (OHRI)	Ottawa	Ontario
Korea, Republic of	National Cancer Center	Ilsandong
Korea, Republic of	Seoul National University Hospital (SNUH)	Junggu
United States	The Billings Clinic	Billings	Montana
United States	Clinical Site 1007	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Sylvester Comprehensive Cancer Center / UMHC	Miami	Florida
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Turnstone Biologics, Corp.	Takeda

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level	Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0	25 months
Primary	Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) when combined with pembrolizumab	Percentage of patients with adverse events by severity as determined by NCI CTCAE v5.0	25 months
Primary	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.	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	4 weeks
Primary	Percentage of overall response rate (ORR) by RECIST 1.1 at the RP2D	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	25 months
Primary	Percentage of overall response rate (ORR) by immunotherapy RECIST (iRECIST) at the RP2D	Percentage of patients treated at the RP2D with pembrolizumab with a partial response (PR) or complete response (CR) by iRECIST following central radiologist review	25 months
Secondary	Number and severity of adverse events at the RP2D	Number of patients with adverse events by severity and frequency as determined by NCI CTCAE v5.0	25 months
Secondary	Median overall survival (OS)	Median overall survival in months in patients	48 months
Secondary	Median Duration of Response (DoR)	Median duration of response in patients with a CR or PR	25 months
Secondary	Proportion of patients with a response (ORR)	Percentage of patients in all arms with a CR or PR as assessed by the central radiologist using RECIST 1.1 and iRECIST	25 months
Secondary	Median Disease Control Rate (DCR)	Median duration of response in patients with a CR, PR, or stable disease (SD)	25 months
Secondary	Time to tumor progression (TTP)	Median time until patient disease progression (PD)	25 months
Secondary	Median progression free survival	Median duration of progression free survival of patients	25 months