Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients
Phase 2 Trial of Voyager VI (Vesicular Stomatitis Virus Expressing NIS and Human Interferon Beta, VV1), in Combination With Cemiplimab in Patients With Select Solid Tumors
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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BR
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Salvador, BR, Brazil, 41253-190
- Hospital Sao Rafael
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brazil, 90035-000
- Hospital Moinhos de Vento
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Rio de Janeiro
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Rio de Janeiro, Rio de Janeiro, Brazil, 20231-050
- INCA
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São Paulo
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Barretos, São Paulo, Brazil, 14.784-400
- Hospital de Amor de Barretos
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-
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California
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Santa Monica, California, United States, 90404
- Saint John's Health Center - John Wayne Cancer Institute (JWCI)
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Connecticut
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New Haven, Connecticut, United States, 06520-8032
- Yale University
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Florida
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Miami, Florida, United States, 33136
- University of Miami
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Ochsner Clinic Foundation
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Montana
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Billings, Montana, United States, 59101
- Billings Clinic Montana Cancer Consortium
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New York
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New York, New York, United States, 10029
- Icahn School Of Medicine At Mount Sinai
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Ohio
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Cincinnati, Ohio, United States, 45219
- University of Cincinnati Medical Center
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South Dakota
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Sioux Falls, South Dakota, United States, 57104
- Sanford Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion:
- Age ≥18 years on day of signing informed consent.
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.
- At least one tumor lesion amenable to IT injection and biopsy that has not been previously irradiated.
- Measurable disease based on RECIST 1.1., including ≥ 1 measurable lesion(s) to be injected
- Performance status of 0 or 1 on the ECOG Performance Scale
- Life expectancy of >3 months.
- Willingness to provide biological samples required for the duration of the study, including a fresh tumor biopsy sample whilst on study.
- 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:
- Availability of and patient acceptance of an alternative curative therapeutic option.
- Patients with tumor lesion(s) > 5cm in diameter.
- 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.
- Patients who have a diagnosis of ocular, mucosal or acral melanoma.
- Known seropositivity for and with active infection with HIV.
- Seropositive for and with evidence of active viral infection with HBV.
- Seropositive for and with active viral infection with HCV.
- Known history of active or latent TB.
- 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).
Prior therapy within the following timeframe before the planned start of study treatment as follows:
- Small molecule inhibitors, and/or other investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter.
- Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter.
- Radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
- 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).
- 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
- Immunodeficiency or immunosuppression, including systemic corticosteroids at >10 mg/day prednisone or equivalent within 1 week prior to planned start of study treatment.
- History of Grade 3 or 4 immune-mediated adverse reaction to immune CPIs.
- Toxicities from previous therapies that have not resolved to a Grade 1 or less.
- History of non-infectious pneumonitis that required steroids, or current pneumonitis.
- High volume disease, as assessed clinically by the medical monitor via parameters such as radiologic impression and tumor markers or lactate dehydrogenase (LDH).
- 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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
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.
|
Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.
Other Names:
VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit
Other Names:
|
|
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.
|
Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.
Other Names:
VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit
Other Names:
|
|
Experimental: Melanoma intratumoral
(CLOSED): 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.
|
Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.
Other Names:
VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Objective response rate (ORR) per imaging assessment
Time Frame: within 24 months
|
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
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within 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v5.0
Time Frame: within 24 months
|
Safety and tolerability
|
within 24 months
|
|
Serum concentration time
Time Frame: within 24 months
|
Serum concentration time data using RT-PCR of VSV-IFNβ-NIS and systemic cemiplimab levels
|
within 24 months
|
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To investigate the pharmacodynamics (PD) of VV1 by measuring serum IFNβ
Time Frame: within 24 months
|
To investigate the pharmacodynamics (PD) of VV1 by measuring serum IFNβ expression
|
within 24 months
|
Collaborators and Investigators
Sponsor
Collaborators
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)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Intestinal Diseases
- Neoplasms by Histologic Type
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Digestive System Diseases
- Gastrointestinal Diseases
- Colorectal Neoplasms
- Intestinal Neoplasms
- Head and Neck Neoplasms
- Neoplasms, Glandular and Epithelial
- Colonic Diseases
- Skin Diseases
- Carcinoma
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Skin Neoplasms
- Carcinoma, Squamous Cell
- Skin and Connective Tissue Diseases
- Squamous Cell Carcinoma of Head and Neck
- Colonic Neoplasms
- Melanoma
- 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)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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