Clinical trial NCT04301011: Study of TBio-6517 Given 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 Alone and in Combination With Pembrolizumab, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Keywords: Renal Cell
CRC
MSS-CRC
Oncolytic Virus
Intratumoral injection
HPV cancer
cervical cancer
mesothelioma
melanoma
skin cancer
oropharyngeal
Lead sponsor: Turnstone Biologics, Corp.
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2020-03-09
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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. 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

Primary outcomes:
measure: Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level
timeFrame: 25 months
measure: Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) when combined with pembrolizumab
timeFrame: 25 months
measure: 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.
timeFrame: 4 weeks
measure: Percentage of overall response rate (ORR) by RECIST 1.1 at the RP2D
timeFrame: 25 months
measure: Percentage of overall response rate (ORR) by immunotherapy RECIST (iRECIST) at the RP2D
timeFrame: 25 months
Secondary outcomes:
measure: Number and severity of adverse events at the RP2D
timeFrame: 25 months
measure: Median overall survival (OS)
timeFrame: 48 months
measure: Median Duration of Response (DoR)
timeFrame: 25 months
measure: Proportion of patients with a response (ORR)
timeFrame: 25 months
measure: Median Disease Control Rate (DCR)
timeFrame: 25 months
measure: Time to tumor progression (TTP)
timeFrame: 25 months
measure: Median progression free survival
timeFrame: 25 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center / UMHC
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Clinical Site 1007
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Billings
country: United States
facility: The Billings Clinic
state: Montana
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Ottawa
country: Canada
facility: Ottawa Hospital and Research Institute (OHRI)
state: Ontario
city: Ilsandong
country: Korea, Republic of
facility: National Cancer Center
city: Junggu
country: Korea, Republic of
facility: Seoul National University Hospital (SNUH)
Study officials:
affiliation: Turnstone Biologics
name: Ines Verdon, MD
role: STUDY_DIRECTOR
References: