Clinical Trials /

A Study of Recombinant Vaccinia Virus in Combination With REGN2810 for Renal Cell Carcinoma

NCT03294083

Description:

This is a Phase 1b, open-label, multi-center, dose-escalation trial of Pexa-Vec plus REGN2810 in patients with metastatic or unresectable renal cell carcinoma (RCC). The trial consists of a dose-escalation stage, where the maximum feasible dose of Pexa-Vec in combination with REGN2810 will be determined, followed by an expansion stage. During the expansion patients will receive REGN2810 alone or in combination with Pexa-Vec, which will be administered either through intravenous (IV) or intratumoral (IT) injection.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Recombinant Vaccinia Virus in Combination With REGN2810 for Renal Cell Carcinoma
  • Official Title: A Phase 1b, Dose-escalation Study of Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) in Combination With REGN2810 (Anti-PD-1) in Patients With Metastatic or Unresectable Renal Cell Carcinoma (RCC)

Clinical Trial IDs

  • ORG STUDY ID: JX594-REN026
  • NCT ID: NCT03294083

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
Pexastimogene Devacirepvec (Pexa-Vec)JX-594Part 1, Dose escalation
REGN2810Part 1, Dose escalation

Purpose

This is a Phase 1b, open-label, multi-center, dose-escalation trial of Pexa-Vec plus REGN2810 in patients with metastatic or unresectable renal cell carcinoma (RCC). The trial consists of a dose-escalation stage, where the maximum feasible dose of Pexa-Vec in combination with REGN2810 will be determined, followed by an expansion stage. During the expansion patients will receive REGN2810 alone or in combination with Pexa-Vec, which will be administered either through intravenous (IV) or intratumoral (IT) injection.

Trial Arms

NameTypeDescriptionInterventions
Part 1, Dose escalationExperimentalPexa-Vec will be administered via IV infusion at a dose of 3 x 10^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10^9 pfu. REGN2810 will be administered via IV infusion every 3 weeks.
  • Pexastimogene Devacirepvec (Pexa-Vec)
  • REGN2810
Part 2, Pexa-Vec (IT) and REGN2810ExperimentalPexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. REGN2810 will be administered via IV infusion every 3 weeks.
  • Pexastimogene Devacirepvec (Pexa-Vec)
  • REGN2810
Part 2, REGN2810ExperimentalREGN2810 will be administered via IV infusion every 3 weeks. At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. REGN2810 will continue every 3 weeks.
  • REGN2810
Part 2, Pexa-Vec (IV) and REGN2810ExperimentalPexa-Vec will be administered via IV infusion once per week for 4 treatments. REGN2810 will be administered via IV infusion every 3 weeks.
  • Pexastimogene Devacirepvec (Pexa-Vec)
  • REGN2810

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic or unresectable clear cell renal
             cell carcinoma (ccRCC)

          -  Measurable disease based on RECIST 1.1 criteria. Tumor lesions situated in a
             previously irradiated area are considered measurable if progression has been
             demonstrated in such lesions

          -  Karnofsky performance status of 70-100

          -  Age ≥20 years old (or appropriate age of consent for the region)

          -  Adequate hematological, hepatic, and renal function

        Exclusion Criteria:

          -  Known significant immunodeficiency due to underlying illness (e.g., human
             immunodeficiency virus [HIV] / acquired immune deficiency syndrome [AIDS]) and/or
             immune-suppressive medication including high-dose corticosteroids

          -  Part 2 only: Prior treatment with any anti-cancer immunotherapy, including therapy
             with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (prior IL-2 or interferon allowed)
             . For Part 1: patients are excluded if they were intolerant to anti-PD-1 or anti-PD-L1
             targeted therapies

          -  Major surgery within 4 weeks of study treatment (minor surgical procedures are
             allowed)

          -  Ongoing severe inflammatory skin condition requiring prior medical treatment

          -  History of eczema requiring prior medical treatment

          -  Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key
             anatomical structure (e.g., pulmonary airway) OR viable central nervous system
             malignancy

          -  Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural
             effusions.

          -  Symptomatic cardiovascular disease, including but not limited to significant coronary
             artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure
             within the preceding 12 months.

          -  Asymptomatic cardiovascular disease (current or past history) unless cardiology
             consultation and clearance has been obtained for study participation.

          -  Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to
             and 48 hours after all Pexa-Vec treatments

          -  Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be
             discontinued within 14 days prior to any Pexa-Vec dose

          -  Known active Hepatitis B or Hepatitis C
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)
Time Frame:36 days after first treatment
Safety Issue:
Description:MTD/MFD of Pexa-Vec administered by IV infusion in combination with REGN2810

Secondary Outcome Measures

Measure:Progression free survival
Time Frame:Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Safety Issue:
Description:
Measure:Best radiographic response
Time Frame:Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SillaJen, Inc.

Trial Keywords

  • Cancer
  • Renal cell carcinoma
  • Clear cell renal cell carcinoma

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