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

Primary Purpose

Solid Tumor, Microsatellite Stable Colorectal Cancer, HPV Positive Oropharyngeal Squamous Cell Carcinoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TBio-6517
Pembrolizumab
Sponsored by
Turnstone Biologics, Corp.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring Renal Cell, CRC, MSS-CRC, Oncolytic Virus, Intratumoral injection, HPV cancer, cervical cancer, mesothelioma, melanoma, skin cancer, oropharyngeal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • Mayo Clinic
  • Sylvester Comprehensive Cancer Center / UMHC
  • University of Kansas Medical Center
  • Clinical Site 1007
  • Mayo Clinic
  • The Billings Clinic
  • University of Texas MD Anderson Cancer Center
  • Ottawa Hospital and Research Institute (OHRI)
  • National Cancer Center
  • Seoul National University Hospital (SNUH)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm A: TBio-6517 alone

Arm B: TBio-6517 and Pembrolizumab

TBio-6517 and Pembrolizumab in MSS-CRC

TBio-6517 and Pembrolizumab in cutaneous melanoma

TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin

TBio-6517 and Pembrolizumab in HPV positive head and neck cancer

Arm C: TBio-6517 intravenous

Arm D: TBio-6517 intravenous and Pembrolizumab

Arm Description

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.

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.

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.

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.

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.

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.

Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months.

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.

Outcomes

Primary Outcome Measures

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
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
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
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
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

Secondary Outcome Measures

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
Median overall survival (OS)
Median overall survival in months in patients
Median Duration of Response (DoR)
Median duration of response in patients with a CR or PR
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
Median Disease Control Rate (DCR)
Median duration of response in patients with a CR, PR, or stable disease (SD)
Time to tumor progression (TTP)
Median time until patient disease progression (PD)
Median progression free survival
Median duration of progression free survival of patients

Full Information

First Posted
March 4, 2020
Last Updated
March 9, 2023
Sponsor
Turnstone Biologics, Corp.
Collaborators
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT04301011
Brief Title
Study of TBio-6517 Given Alone or in Combination With Pembrolizumab in Solid Tumors
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2, 2020 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Turnstone Biologics, Corp.
Collaborators
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: TBio-6517 alone
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B: TBio-6517 and Pembrolizumab
Arm Type
Experimental
Arm Description
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 Title
TBio-6517 and Pembrolizumab in MSS-CRC
Arm Type
Experimental
Arm Description
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.
Arm Title
TBio-6517 and Pembrolizumab in cutaneous melanoma
Arm Type
Experimental
Arm Description
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 Title
TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin
Arm Type
Experimental
Arm Description
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 Title
TBio-6517 and Pembrolizumab in HPV positive head and neck cancer
Arm Type
Experimental
Arm Description
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 Title
Arm C: TBio-6517 intravenous
Arm Type
Experimental
Arm Description
Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months.
Arm Title
Arm D: TBio-6517 intravenous and Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
TBio-6517
Other Intervention Name(s)
RIVAL-01
Intervention Description
Engineered Oncolytic Vaccinia Virus
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Immune checkpoint inhibitor.
Primary Outcome Measure Information:
Title
Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level
Description
Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0
Time Frame
25 months
Title
Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) when combined with pembrolizumab
Description
Percentage of patients with adverse events by severity as determined by NCI CTCAE v5.0
Time Frame
25 months
Title
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.
Description
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
Time Frame
4 weeks
Title
Percentage of overall response rate (ORR) by RECIST 1.1 at the RP2D
Description
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
Time Frame
25 months
Title
Percentage of overall response rate (ORR) by immunotherapy RECIST (iRECIST) at the RP2D
Description
Percentage of patients treated at the RP2D with pembrolizumab with a partial response (PR) or complete response (CR) by iRECIST following central radiologist review
Time Frame
25 months
Secondary Outcome Measure Information:
Title
Number and severity of adverse events at the RP2D
Description
Number of patients with adverse events by severity and frequency as determined by NCI CTCAE v5.0
Time Frame
25 months
Title
Median overall survival (OS)
Description
Median overall survival in months in patients
Time Frame
48 months
Title
Median Duration of Response (DoR)
Description
Median duration of response in patients with a CR or PR
Time Frame
25 months
Title
Proportion of patients with a response (ORR)
Description
Percentage of patients in all arms with a CR or PR as assessed by the central radiologist using RECIST 1.1 and iRECIST
Time Frame
25 months
Title
Median Disease Control Rate (DCR)
Description
Median duration of response in patients with a CR, PR, or stable disease (SD)
Time Frame
25 months
Title
Time to tumor progression (TTP)
Description
Median time until patient disease progression (PD)
Time Frame
25 months
Title
Median progression free survival
Description
Median duration of progression free survival of patients
Time Frame
25 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ines Verdon, MD
Organizational Affiliation
Turnstone Biologics
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Sylvester Comprehensive Cancer Center / UMHC
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Clinical Site 1007
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
The Billings Clinic
City
Billings
State/Province
Montana
ZIP/Postal Code
31031
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Ottawa Hospital and Research Institute (OHRI)
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
National Cancer Center
City
Ilsandong
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Seoul National University Hospital (SNUH)
City
Junggu
ZIP/Postal Code
03080
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

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