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

• ClinicalTrials.gov Identifier: NCT04291105
• Recruitment Status: Recruiting
• First Posted: March 2, 2020
• Last Update Posted: January 7, 2021
• Sponsor: Vyriad, Inc.
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Vyriad, Inc.

Tracking Information

• First Submitted Date: February 25, 2020
• First Posted Date: March 2, 2020
• Last Update Posted Date: January 7, 2021
• Actual Study Start Date: April 24, 2020
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 28, 2020)

• Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v5.0 [ Time Frame: within 24 months ]
  Safety and tolerability
• Serum concentration time [ Time Frame: within 24 months ]
  Serum concentration time data using RT-PCR of VSV-IFNβ-NIS and systemic cemiplimab levels
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients
• Official Title: Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Patients With Hepatocellular Carcinoma, Non-Small Cell Lung Cancer, Melanoma or Endometrial Carcinoma
• Brief 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 concurrently enroll patients with four distinct advanced malignancies in 5 separate tumor cohorts. The four cancers type are NSCLC and melanoma that are progressing on CPI treatment, CPI-naïve HCC, and treatment-naïve Endometrial.
• Detailed Description: Patients with melanoma will be enrolled into two parallel cohorts; in one cohort (Intravenous melanoma cohort) patients will receive IV VV1 and patients in the other cohort (Intratumoral melanoma cohort) will receive both IV VV1 and Intratumoral VV1; both cohorts will receive IV cemiplimab in combination therapy with VV1 treatment. Patients with NSCLC, HCC or endometrial cancer will receive IV VV1 and IV cemiplimab combination therapy.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Melanoma
• Hepatocellular Carcinoma
• Non Small Cell Lung Cancer
• Endometrial Cancer

Intervention

• Biological: VV1
  VV1 is to be administered on Day 1
  Other Name: VSV-IFNβ-NIS, Voyager V1
• Biological: Cemiplimab
  Cemiplimab should be given on Day 1 of each 21-day cycle for up to 2 years
  Other Name: Libtayo

Study Arms

• Experimental: Melanoma intratumoral
  Melanoma, IV & IT VV1 + cemiplimab Patients will receive both intravenous (IV) VV1 and intratumoral (IT) VV1 on Day 1. Will also receveive an infusion of cemiplimab on Day 1.
  Interventions:

  • Biological: VV1
  • Biological: Cemiplimab
• Experimental: Melanoma
  Melanoma, IV + cemiplimab Patients will receive both IV VV1 and cemiplimab on Day 1.
  Interventions:

  • Biological: VV1
  • Biological: Cemiplimab
• Experimental: Hepatocellular carcinoma
  Hepatocellular carcinoma Patients will receive both IV VV1 and cemiplimab on Day 1.
  Interventions:

  • Biological: VV1
  • Biological: Cemiplimab
• Experimental: Non-small cell lung cancer
  Non-small cell lung cancer Patients will receive both IV VV1 and cemiplimab on Day 1.
  Interventions:

  • Biological: VV1
  • Biological: Cemiplimab
• Experimental: Endometrial cancer
  Endometrial cancer Patients will receive both IV VV1 and cemiplimab on Day 1.
  Interventions:

  • Biological: VV1
  • Biological: Cemiplimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 28, 2020): 152
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2023
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria

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

2. Specific by tumor cohorts:

   • For the HCC cohort, confirmed diagnosis of inoperable HCC by histology or clinical/radiological criteria. i. No prior therapy with a PD-(L)1 immune checkpoint inhibitor (CPI) (prior sorafenib is permitted). ii. No or one prior line of systemic therapy only. iii. Child Pugh Score A or B7.
   • For the NSCLC cohort, histologically confirmed diagnosis of advanced and/or metastatic NSCLC in which radiological progression has been demonstrated during therapy with a PD(L)1 immune CPI and for which no existing options are felt to provide clinical benefit (only one line of PD-(L)1 therapy is permitted).

   Progression during or following 1 or more prior regimen(s) and no more than 3 prior therapeutic regimens for metastatic disease.

   • For the melanoma cohorts, histologically confirmed diagnosis of advanced and/or metastatic melanoma in which radiological progression has been demonstrated during therapy with a PD(L)1 immune CPI and for which no existing options are considered to provide clinical benefit (only one line of PD(L)1 therapy is permitted). Progression on ipilimumab is not required. Note: For IT melanoma cohort:

     • i. At least one tumor lesion amenable to repeated IT injection via palpation or ultrasound. Injection of deep visceral lesions is not permitted.
     • ii. Agrees to provide a newly obtained biopsy of injected and witness lesions prior to start of study treatment, and to repeat biopsies twice during study treatment, and to providing the acquired tissue for biomarker analysis. Tissue obtained for the biopsy must not be previously irradiated, but a new or progressing lesion in the radiation field is acceptable.
   • For the endometrial cancer cohort, histologically confirmed diagnosis of advanced and/or metastatic endometrioid endometrial adenocarcinoma. Eligible patients will not have had any prior systemic therapy in the metastatic setting.

3. For patients treated with prior anti-PD-(L)1 therapy:

   • Last dose of anti-PD-(L)1 must be within 12 weeks of initiating study treatment.
   • Patient must have received at least 4 doses on q2w, 3 doses on q3w or 2 doses on q4w schedule of the previous anti-PD-(L)1 therapy.
   • Progression on prior anti-PD-(L)1 therapy must be defined by:
   • Documented radiographic progression on a single radiographic scan, if treatment with anti-PD-(L)1 was ≥ 16 weeks.
   • Documented radiographic progression on two consecutive radiographic scans at least 4 weeks apart, if treatment with anti-PD-(L)1 therapy was between 8 - 16 weeks; if radiographic progression is accompanied with clinical progression, then a single scan assessment may be used.
   • If progression was only in lymph nodes, biopsy to provide histological confirmation of progression in the lymph node is required.
4. Measurable disease based on RECIST 1.1.

Key Exclusion criteria: 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 National Institute of Cancer Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE, v5.0) viral, bacterial, or fungal infection within 2 weeks of registration.

3. Known seropositivity for and with active infection by the human immunodeficiency virus (HIV).

   • Patients who are seropositive for HIV but are receiving antiviral therapy and show non-detectable viral load and a normal CD4 T cell count for at least 6 months are eligible.

4. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV). Patients who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA negative are eligible.

   • Patients who had HBV but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible.
   • Patients who are seropositive because of HBV vaccine are eligible.

5. Seropositive for and with active viral infection with hepatitis C virus (HCV).

   • Patients who had HCV but have received an antiviral treatment and show no detectable HCV viral DNA for 6 months are eligible.

6. Known history of active or latent TB (bacillus tuberculosis).
7. 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).

8. 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.
   • Antibody drug conjugates and radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
9. New York Heart Association (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 supraventricular tachycardia).
10. 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.
11. Immunodeficiency or immunosuppression
12. History of Grade 3 or 4 immune-mediated adverse reaction to immune CPIs.
13. Toxicities from previous therapies that have not resolved to a Grade 1 or less.
14. History of non-infectious pneumonitis that required steroids, or current pneumonitis.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Steve Kaesshaefer; +19737152917; steve.kaesshaefer@Bexonclinical.com

Contact: Barbara Duckett; 5072890944; bduckett@vyriad.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04291105
• Other Study ID Numbers: VYR-VSV2-203
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Vyriad, Inc.
• Study Sponsor: Vyriad, Inc.
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Chair: Alice Bexon, MD; CMO
• Study Director: Naimish Pandya, MD; Clinical Lead

• PRS Account: Vyriad, Inc.
• Verification Date: January 2021