NCT04301011

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).

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
27

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2020

Typical duration for phase_1

Geographic Reach
3 countries

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 4, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 9, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

June 2, 2020

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 23, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 23, 2023

Completed
Last Updated

April 23, 2025

Status Verified

April 1, 2025

Enrollment Period

2.6 years

First QC Date

March 4, 2020

Last Update Submit

April 17, 2025

Conditions

Keywords

Renal CellCRCMSS-CRCOncolytic VirusIntratumoral injectionHPV cancercervical cancermesotheliomamelanomaskin canceroropharyngeal

Outcome Measures

Primary Outcomes (5)

  • 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

  • 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

  • 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

  • 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

  • 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 Outcomes (7)

  • Number and severity of adverse events at the RP2D

    25 months

  • Median overall survival (OS)

    48 months

  • Median Duration of Response (DoR)

    25 months

  • Proportion of patients with a response (ORR)

    25 months

  • Median Disease Control Rate (DCR)

    25 months

  • +2 more secondary outcomes

Study Arms (8)

Arm A: TBio-6517 alone

EXPERIMENTAL

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

Arm B: TBio-6517 and Pembrolizumab

EXPERIMENTAL

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-6517Biological: Pembrolizumab

TBio-6517 and Pembrolizumab in MSS-CRC

EXPERIMENTAL

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-6517Biological: Pembrolizumab

TBio-6517 and Pembrolizumab in cutaneous melanoma

EXPERIMENTAL

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-6517Biological: Pembrolizumab

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

EXPERIMENTAL

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-6517Biological: Pembrolizumab

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

EXPERIMENTAL

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-6517Biological: Pembrolizumab

Arm C: TBio-6517 intravenous

EXPERIMENTAL

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

Arm D: TBio-6517 intravenous and Pembrolizumab

EXPERIMENTAL

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-6517Biological: Pembrolizumab

Interventions

TBio-6517BIOLOGICAL

Engineered Oncolytic Vaccinia Virus

Also known as: RIVAL-01
Arm A: TBio-6517 aloneArm B: TBio-6517 and PembrolizumabArm C: TBio-6517 intravenousArm D: TBio-6517 intravenous and PembrolizumabTBio-6517 and Pembrolizumab in HPV positive head and neck cancerTBio-6517 and Pembrolizumab in MSS-CRCTBio-6517 and Pembrolizumab in cutaneous melanomaTBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin
PembrolizumabBIOLOGICAL

Immune checkpoint inhibitor.

Also known as: Keytruda
Arm B: TBio-6517 and PembrolizumabArm D: TBio-6517 intravenous and PembrolizumabTBio-6517 and Pembrolizumab in HPV positive head and neck cancerTBio-6517 and Pembrolizumab in MSS-CRCTBio-6517 and Pembrolizumab in cutaneous melanomaTBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center / UMHC

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66205, United States

Location

Clinical Site 1007

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

The Billings Clinic

Billings, Montana, 31031, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Ottawa Hospital and Research Institute (OHRI)

Ottawa, Ontario, Canada

Location

National Cancer Center

Ilsandong, 10408, South Korea

Location

Seoul National University Hospital (SNUH)

Junggu, 03080, South Korea

Location

MeSH Terms

Conditions

Uterine Cervical NeoplasmsMelanomaMesotheliomaCarcinoma, Renal CellOropharyngeal NeoplasmsSkin Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Nerve TissueNevi and MelanomasSkin DiseasesSkin and Connective Tissue DiseasesAdenomaNeoplasms, Glandular and EpithelialNeoplasms, MesothelialAdenocarcinomaCarcinomaKidney NeoplasmsUrologic NeoplasmsKidney DiseasesUrologic DiseasesMale Urogenital DiseasesPharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsHead and Neck NeoplasmsPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Study Officials

  • Ines Verdon, MD

    Turnstone Biologics

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 4, 2020

First Posted

March 9, 2020

Study Start

June 2, 2020

Primary Completion

January 23, 2023

Study Completion

January 23, 2023

Last Updated

April 23, 2025

Record last verified: 2025-04

Locations