Phase 2 Trial of Voyager V1 in Combination with Cemiplimab in Cancer Patients

Phase 2 Trial of Voyager V1 in Combination with Cemiplimab in Patients with Select Solid Tumors

This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with cemiplimab. The study will enroll patients with three distinct separate tumor cohorts. The cancers types are colorectal, head and neck carcinoma, and melanoma that are progressing on CPI treatment.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Head and Neck Squamous Cell Carcinoma; Colo-rectal Cancer
• Intervention / Treatment: Biological: Cemiplimab; Biological: VV1

Detailed Description

Patients enrolled into three parallel doublet cohorts with an optimal Simon's two stage design. Patients will receive Voyager V1 as a direct to tumor injection (IT) in all 3 cancer groups and cemiplimab via IV infusion. Patients will return for treatment every 3 weeks until lack of clinical benefit or limiting toxicity. Efficacy evaluations will be conducted every 6 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 87
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jennifer Boughton; Phone Number: 9085533135; Email: JBoughton@vyriad.com

Study Locations

• Brazil
  • BR
    • Salvador, BR, Brazil, 41253-190
      • Recruiting
      • Hospital Sao Rafael
      • Contact: Fernanda Coelho
      • Contact: Rodrigo Guedes, MD
  • RJ
    • Rio De Janeiro, RJ, Brazil, 20231-050
      • Recruiting
      • INCA
      • Contact: Alexssandra Lima, MD; Phone Number: 55 21 3207-2988; Email: Falves@inca.gov.br
  • RS
    • Porto Alegre, RS, Brazil, 90035-000
      • Recruiting
      • Hospital Moinhos de Vento
      • Contact: Fabio Franke, MD; Phone Number: 51-33142965
      • Contact: Desiree Deconte; Email: desiree.deconte@hmv.org.br
  • SP
    • Barretos, SP, Brazil, 14.784-400
      • Active, not recruiting
      • Hospital de Amor de Barretos
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Withdrawn
      • Mayo Clinical
  • California
    • Durate, California, United States, 91010
      • Withdrawn
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90033
      • Withdrawn
      • USC Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92663
      • Withdrawn
      • Hoag Memorial Hospital Presbyterian
    • Santa Monica, California, United States, 90404
      • Terminated
      • Saint John's Health Center - John Wayne Cancer Institute (JWCI)
    • Stanford, California, United States, 94305
      • Withdrawn
      • Stanford Health Care
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8032
      • Recruiting
      • Yale University
      • Contact: Barbara Johnson; Email: barbara.johnson@yale.edu
      • Contact: Mario Sznol, MD
      • Contact: Neta Shanwetter Levit, MPH; Phone Number: 203.500.0834; Email: Neta.shanwetterlevit@yale.edu
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Withdrawn
      • Georgetown University Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Withdrawn
      • Mayo Clinical
    • Miami, Florida, United States, 33136
      • Completed
      • University of Miami
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Ochsner Clinic Foundation
      • Contact: Daniel Johnson, MD
      • Contact: Amanda Woolery, RN, BSN; Phone Number: 504-842-0275.; Email: amanda.woolery@ochsner.org
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Withdrawn
      • Massachusetts General Hospital Cancer Center
  • Minnesota
    • Minneapolis,, Minnesota, United States, 55455
      • Withdrawn
      • Masonic Cancer Center, University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Clinical Trials Referal Office; Phone Number: 855-776-0015
      • Contact: Patrick McGarrah, MD
  • Montana
    • Billings, Montana, United States, 59101
      • Terminated
      • Billings Clinic Montana Cancer Consortium
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Withdrawn
      • Atlantic Health
    • New Brunswick, New Jersey, United States, 08901
      • Withdrawn
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • ICAHN School of Medicine at Mount Sinai
      • Contact: Ashley Poliak Hammad, MSN; Phone Number: 212-824-7309; Email: Ashley.hammad@mssm.edu
      • Contact: Thomas Marron, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
      • Contact: Trisha Wise-Draper, MD, PhD; Phone Number: 513-584-7698; Email: cancer@uchealth.com
    • Columbus, Ohio, United States, 43210
      • Withdrawn
      • Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Withdrawn
      • UPMC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Cancer Center
      • Contact: Staci Vogel; Phone Number: 605-312-3320; Email: staci.vogel@sanfordhealth.org
      • Contact: Steven Powell, MD
  • Texas
    • San Antonio, Texas, United States, 78229
      • Withdrawn
      • UT Health San Antonio MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

1. Age ≥18 years on day of signing informed consent.

2. Specific by tumor cohorts:

   a. For the HSNCC cohort, histologically confirmed diagnosis of advanced and/or metastatic HSNCC suitable for first line immunotherapy.

   i. HPV+ and HPV- patients are allowed.

   ii. Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology) or salivary gland tumors.

   iii. PD-L1 status ≥ 1% per local CPS score. Samples should be provided to central lab for post-hoc centralized testing.

   iv. At least 12 months between last dose of prior adjuvant therapy and date of relapse diagnosis (if given). For the purposes of this protocol, "prior adjuvant therapy" only applies to full dose systemic chemotherapy (such as pre-operative systemic induction chemotherapy), but does not include radiation + surgery, or radiation + low or partial dose platinum radiosensitization. There is no time limit (washout) between the end of any prior radiation/ chemoradiation and the start of study drug v. No prior anti-PD-(L)1 treatment for HNSCC.

   b. For the melanoma cohorts, histologically confirmed diagnosis of advanced and/or metastatic cutaneous melanoma for which no existing options are considered to provide clinical benefit.

   i. Best response of uPR, SD or PD to an anti-PD-(L)1-containing regimen.

   ii. Prior anti-PD-(L)1 therapy must have lasted ≥ 12 weeks.

   iii. Radiological progression was demonstrated during or after therapy with a PD-(L)1 immune CPI (only one prior line of PD-(L)1 therapy is permitted.

   iv. If patient received anti-PD-1 as prior adjuvant therapy, patient should have relapsed during therapy or within the subsequent 6 months after last dose. Note: Progression on ipilimumab is not required.

   v. Patients with BRAF V600-positive tumor(s) should have received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) in addition to treatment with an anti-PD-1 or to have declined targeted therapy. Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms nor evidence of rapidly progressive disease are not required to be treated with a BRAF inhibitor (alone or in combination with a MEK inhibitor) based on investigator's decision

   c. For the CRC cohort, a histologically confirmed diagnosis of advanced and/or metastatic CRC.

   i. Received or are not eligible for standard of care fluoropyrimidine(s), oxaliplatin, irinotecan, anti-VEGF and EGFR-targeted therapies.

   ii. Non-microsatellite instability high (non-MSI high).

   iii. Progression on previous systemic therapy.

3. At least one tumor lesion amenable to IT injection and biopsy that has not been previously irradiated.
4. Measurable disease based on RECIST 1.1., including ≥ 1 measurable lesion(s) to be injected
5. Performance status of 0 or 1 on the ECOG Performance Scale
6. Life expectancy of >3 months.
7. Willingness to provide biological samples required for the duration of the study, including a fresh tumor biopsy sample whilst on study.
8. Adequate organ function assessed by laboratory values obtained ≤14 days prior to enrollment

Exclusion:

Patients meeting any of the following exclusion criteria at screening/Day -1 of first dosing will not be enrolled in the study:

1. Availability of and patient acceptance of an alternative curative therapeutic option.
2. Patients with tumor lesion(s) > 5cm in diameter.
3. Recent or ongoing serious infection, including any active Grade 3 or higher per the NCI CTCAE, v5.0 viral, bacterial, or fungal infection within 2 weeks of registration.
4. Patients who have a diagnosis of ocular, mucosal or acral melanoma.
5. Known seropositivity for and with active infection with HIV.
6. Seropositive for and with evidence of active viral infection with HBV.
7. Seropositive for and with active viral infection with HCV.
8. Known history of active or latent TB.
9. Any concomitant serious health condition, which, in the opinion of the investigator, would place the patient at undue risk from the study, including uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).

10. Prior therapy within the following timeframe before the planned start of study treatment as follows:

    1. Small molecule inhibitors, and/or other investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter.
    2. Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter.
    3. Radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
11. NYHA classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or SVT).
12. Any known or suspected active organ-threatening autoimmune disease, such as inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis, with the exception of hypothyroidism and type 1 diabetes that are controlled with treatment
13. Immunodeficiency or immunosuppression, including systemic corticosteroids at >10 mg/day prednisone or equivalent within 1 week prior to planned start of study treatment.
14. History of Grade 3 or 4 immune-mediated adverse reaction to immune CPIs.
15. Toxicities from previous therapies that have not resolved to a Grade 1 or less.
16. History of non-infectious pneumonitis that required steroids, or current pneumonitis.
17. High volume disease, as assessed clinically by the medical monitor via parameters such as radiologic impression and tumor markers or lactate dehydrogenase (LDH).
18. Portal vein thrombosis involving more than intrahepatic portal vein branches: thrombosis of the right or left portal vein branch or the bifurcation, partial or complete obstruction of the portal vein trunk.

18.19. Known concurrent malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melanoma intratumoral; Melanoma, IT VV1 + IV cemiplimab Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.	Biological: Cemiplimab; Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.; Other Names: Libtayo; Biological: VV1; VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit; Other Names: VSV-IFNβ-NIS, Voyager V1, VV1
Experimental: Head and Neck SCC intratumoral; HNSCC, IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.	Biological: Cemiplimab; Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.; Other Names: Libtayo; Biological: VV1; VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit; Other Names: VSV-IFNβ-NIS, Voyager V1, VV1
Experimental: Colo-rectal Carcinoma intratumoral (Arm closed); (CLOSED) IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.	Biological: Cemiplimab; Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.; Other Names: Libtayo; Biological: VV1; VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit; Other Names: VSV-IFNβ-NIS, Voyager V1, VV1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) per imaging assessment	Percentage of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through disease progression, by investigator review based on RECIST version 1.1	within 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v5.0	Safety and tolerability	within 24 months
Serum concentration time	Serum concentration time data using RT-PCR of VSV-IFNβ-NIS and systemic cemiplimab levels	within 24 months
To investigate the pharmacodynamics (PD) of VV1 by measuring serum IFNβ	To investigate the pharmacodynamics (PD) of VV1 by measuring serum IFNβ expression	within 24 months

Collaborators and Investigators

• Sponsor: Vyriad, Inc.
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Chair: Alice Bexon, MD, CMO; Study Director: Stephen J Russell, MD, Ph.D., Clinical Lead

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Solid Tumor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents, Immunological; Antineoplastic Agents; Cemiplimab
• Other Study ID Numbers: VYR-VSV2-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No