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

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ClinicalTrials.gov Identifier: NCT04301011
Recruitment Status : Recruiting
First Posted : March 9, 2020
Last Update Posted : March 9, 2022
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
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 Biological: TBio-6517 Biological: Pembrolizumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 2, 2020
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : July 30, 2025


Arm Intervention/treatment
Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Experimental: 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.
Biological: TBio-6517
Engineered Oncolytic Vaccinia Virus
Other Name: RIVAL-01

Biological: Pembrolizumab
Immune checkpoint inhibitor.
Other Name: Keytruda




Primary Outcome Measures :
  1. Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) alone at each dose level [ Time Frame: 25 months ]
    Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0

  2. Incidence of adverse events when TBio-6517 administered by direct injection into tumor(s) when combined with pembrolizumab [ Time Frame: 25 months ]
    Percentage of patients with adverse events by severity as determined by NCI CTCAE v5.0

  3. 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. [ Time Frame: 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

  4. Percentage of overall response rate (ORR) by RECIST 1.1 at the RP2D [ Time Frame: 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

  5. Percentage of overall response rate (ORR) by immunotherapy RECIST (iRECIST) at the RP2D [ Time Frame: 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


Secondary Outcome Measures :
  1. Number and severity of adverse events at the RP2D [ Time Frame: 25 months ]
    Number of patients with adverse events by severity and frequency as determined by NCI CTCAE v5.0

  2. Median overall survival (OS) [ Time Frame: 48 months ]
    Median overall survival in months in patients

  3. Median Duration of Response (DoR) [ Time Frame: 25 months ]
    Median duration of response in patients with a CR or PR

  4. Proportion of patients with a response (ORR) [ Time Frame: 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

  5. Median Disease Control Rate (DCR) [ Time Frame: 25 months ]
    Median duration of response in patients with a CR, PR, or stable disease (SD)

  6. Time to tumor progression (TTP) [ Time Frame: 25 months ]
    Median time until patient disease progression (PD)

  7. Median progression free survival [ Time Frame: 25 months ]
    Median duration of progression free survival of patients



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04301011


Contacts
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Contact: Huguette A Graham 613 421-8930 clinicalops@turnstonebio.com

Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact       clinicalops@turnstonebio.com   
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact       clinicalops@turnstonebio.com   
Sylvester Comprehensive Cancer Center / UMHC Recruiting
Miami, Florida, United States, 33136
Contact       clinicalops@turnstonebio.com   
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66205
Contact       clinicalops@turnstonebio.com   
United States, Massachusetts
Clinical Site 1007 Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact       clinicalops@turnstonebio.com   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55902
Contact       clinicalops@turnstonebio.com   
United States, Montana
The Billings Clinic Recruiting
Billings, Montana, United States, 31031
Contact       clinicalops@turnstonebio.com   
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       clinicalops@turnstonebio.com   
Canada, Ontario
Ottawa Hospital and Research Institute (OHRI) Recruiting
Ottawa, Ontario, Canada
Contact       clinicalops@turnstonebio.com   
Korea, Republic of
National Cancer Center Recruiting
Ilsandong, Korea, Republic of, 10408
Contact       clinicalops@turnstonebio.com   
Seoul National University Hospital (SNUH) Recruiting
Junggu, Korea, Republic of, 03080
Contact       clinicalops@turnstonebio.com   
Sponsors and Collaborators
Turnstone Biologics, Corp.
Takeda
Investigators
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Study Director: Justine Walker, MD Turnstone Biologics, Corp.
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Responsible Party: Turnstone Biologics, Corp.
ClinicalTrials.gov Identifier: NCT04301011    
Other Study ID Numbers: TBio-6517-ITu-001
First Posted: March 9, 2020    Key Record Dates
Last Update Posted: March 9, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Turnstone Biologics, Corp.:
Renal Cell
CRC
MSS-CRC
Oncolytic Virus
Intratumoral injection
HPV cancer
cervical cancer
mesothelioma
melanoma
skin cancer
oropharyngeal
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Mesothelioma
Mesothelioma, Malignant
Squamous Cell Carcinoma of Head and Neck
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Adenoma
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Pleural Neoplasms
Lung Diseases