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

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04291105
• Other study ID #: VYR-VSV2-203
• Status: Recruiting
• Phase: Phase 2
• Start date: April 24, 2020
• Est. completion date: March 2025

Study information

• Verified date: October 2023
• Source: Vyriad, Inc.
• Contact: Jennifer boughton
• Phone: 9085533135
• Email: Jboughton[@]vyriad.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 87
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

iii. PD-L1 status = 10% 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). 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. 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.

3. Patients who have a diagnosis of ocular, mucosal or acral melanoma.

4. Known seropositivity for and with active infection with HIV.

5. Seropositive for and with evidence of active viral infection with HBV.

6. Seropositive for and with active viral infection with HCV.

7. Known history of active or latent TB.

8. 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).

9. 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.

10. 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).

11. 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

12. Immunodeficiency or immunosuppression, including systemic corticosteroids at >10 mg/day prednisone or equivalent within 1 week prior to planned start of study treatment.

13. Known concurrent malignancy.

Related Conditions & MeSH terms

• Colo-rectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• VV1
VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit
• Cemiplimab
Cemiplimab should be given on Day 8 of Cycle 1 (28 days) and then Day 1 of each subsequent 21-day cycle.

Locations

Country	Name	City	State
Brazil	Hospital de Amor de Barretos	Barretos	SP
Brazil	Hospital Moinhos de Vento	Porto Alegre	RS
Brazil	INCA	Rio De Janeiro	RJ
United States	Billings Clinic Montana Cancer Consortium	Billings	Montana
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	Mayo Clinical	Jacksonville	Florida
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Atlantic Health	Morristown	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	HOAG Memorial Hospital Presbyterian	Newport Beach	California
United States	Mayo Clinical	Phoenix	Arizona
United States	UPMC	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	UT Health San Antonio MD Anderson Cancer Center	San Antonio	Texas
United States	Saint John's Health Center - John Wayne Cancer Institute (JWCI)	Santa Monica	California
United States	Sanford Cancer Center	Sioux Falls	South Dakota
United States	Stanford Health Care	Stanford	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Vyriad, Inc.	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

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