Clinical Trials /

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

NCT04291105

Description:

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.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: VYR-VSV2-203
  • NCT ID: NCT04291105

Conditions

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

Interventions

DrugSynonymsArms
VV1VSV-IFNβ-NIS, Voyager V1Endometrial cancer
CemiplimabLibtayoEndometrial cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Melanoma intratumoralExperimentalMelanoma, 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.
  • VV1
  • Cemiplimab
MelanomaExperimentalMelanoma, IV + cemiplimab Patients will receive both IV VV1 and cemiplimab on Day 1.
  • VV1
  • Cemiplimab
Hepatocellular carcinomaExperimentalHepatocellular carcinoma Patients will receive both IV VV1 and cemiplimab on Day 1.
  • VV1
  • Cemiplimab
Non-small cell lung cancerExperimentalNon-small cell lung cancer Patients will receive both IV VV1 and cemiplimab on Day 1.
  • VV1
  • Cemiplimab
Endometrial cancerExperimentalEndometrial cancer Patients will receive both IV VV1 and cemiplimab on Day 1.
  • VV1
  • Cemiplimab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) per imaging assessment
Time Frame:within 24 months
Safety Issue:
Description: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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vyriad, Inc.

Trial Keywords

  • Solid Tumor

Last Updated

May 21, 2020