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

NCT ID: NCT04291105

Last Updated: 2025-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-24

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Melanoma Head and Neck Squamous Cell Carcinoma Colo-rectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

VV1

Intervention Type BIOLOGICAL

VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit

Cemiplimab

Intervention Type BIOLOGICAL

Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.

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.

Group Type EXPERIMENTAL

VV1

Intervention Type BIOLOGICAL

VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit

Cemiplimab

Intervention Type BIOLOGICAL

Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.

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.

Group Type EXPERIMENTAL

VV1

Intervention Type BIOLOGICAL

VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit

Cemiplimab

Intervention Type BIOLOGICAL

Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.

Interventions

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VV1

VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit

Intervention Type BIOLOGICAL

Cemiplimab

Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.

Intervention Type BIOLOGICAL

Other Intervention Names

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VSV-IFNβ-NIS, Voyager V1, VV1 Libtayo

Eligibility Criteria

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Inclusion Criteria

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:

Exclusion Criteria

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Vyriad, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alice Bexon, MD

Role: STUDY_CHAIR

CMO

Stephen J Russell, MD, Ph.D.

Role: STUDY_DIRECTOR

Clinical Lead

Locations

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Mayo Clinical

Phoenix, Arizona, United States

Site Status WITHDRAWN

City of Hope Medical Center

Durate, California, United States

Site Status WITHDRAWN

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status WITHDRAWN

HOAG Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status WITHDRAWN

Saint John's Health Center - John Wayne Cancer Institute (JWCI)

Santa Monica, California, United States

Site Status TERMINATED

Stanford Health Care

Stanford, California, United States

Site Status WITHDRAWN

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status WITHDRAWN

Mayo Clinical

Jacksonville, Florida, United States

Site Status WITHDRAWN

University of Miami

Miami, Florida, United States

Site Status COMPLETED

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status WITHDRAWN

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status WITHDRAWN

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Billings Clinic Montana Cancer Consortium

Billings, Montana, United States

Site Status TERMINATED

Atlantic Health

Morristown, New Jersey, United States

Site Status WITHDRAWN

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status WITHDRAWN

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Ohio State University

Columbus, Ohio, United States

Site Status WITHDRAWN

UPMC

Pittsburgh, Pennsylvania, United States

Site Status WITHDRAWN

Sanford Cancer Center

Sioux Falls, South Dakota, United States

Site Status RECRUITING

UT Health San Antonio MD Anderson Cancer Center

San Antonio, Texas, United States

Site Status WITHDRAWN

Hospital Sao Rafael

Salvador, BR, Brazil

Site Status RECRUITING

INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status RECRUITING

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Hospital de Amor de Barretos

Barretos, São Paulo, Brazil

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Brazil

Central Contacts

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Jennifer boughton

Role: CONTACT

9085533135

Facility Contacts

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Neta Shanwetter Levit, MPH

Role: primary

203.500.0834

Barbara Johnson

Role: backup

Amanda Woolery, RN, BSN

Role: primary

504-842-0275.

Clinical Trials Referal Office

Role: primary

855-776-0015

Ashley Poliak Hammad, MSN

Role: primary

212-824-7309

Trisha Wise-Draper, MD, PhD

Role: primary

513-584-7698

Staci Vogel

Role: primary

605-312-3320

Fernanda Coelho

Role: primary

Alexssandra Lima, MD

Role: primary

55 21 3207-2988

Fabio Franke, MD

Role: primary

51-33142965

Desiree Deconte

Role: backup

Other Identifiers

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VYR-VSV2-203

Identifier Type: -

Identifier Source: org_study_id

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