Clinical Trials /

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

NCT03294083

Description:

This is a Phase 1b/2a, open-label, multi-center, dose-escalation and safety/efficacy evaluation trial of Pexa-Vec plus Cemiplimab 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 Cemiplimab will be determined, followed by an expansion stage. During the expansion patients will receive Cemiplimab 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/Phase 2

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)

          -  Part 2 Arm D ONLY: Patients must be refractory to anti PD-1 or anti-PD-L1 (either as
             monotherapy or in-combination with other approved checkpoint inhibitors or targeted
             therapies according to their approved label) and patients must meet all of the
             following criteria:

               1. Received treatment of approved anti PD-1 or anti-PD-L1 (dosed per label of the
                  country providing the clinical site) for at least 12 weeks. History of anti-PD-L1
                  only is not allowed.

               2. Progressive disease after anti PD-1 or anti-PD-L1 will be defined according to
                  RECIST 1.1. The initial evidence of progressive disease is to be confirmed by a
                  second assessment, no less than 4 weeks from the date of the first documented
                  progressive disease, in the absence of rapid clinical progression. (This
                  determination is made by the Investigator; the Sponsor will collect imaging scans
                  for retrospective analysis. Once progressive disease is confirmed, the initial
                  date of progressive disease documentation will be considered the date of disease
                  progression).

               3. Documented disease progression within 12 weeks of the last dose of anti PD-1 or
                  anti-PD-L1. Patients who were re-treated or on maintenance with anti-PD-1 or
                  anti-PD-L1 will be allowed to enter the study as long as there is documented
                  progressive disease within 12 weeks of the last treatment date.

          -  Naive to systemic therapy for RCC or have progressed after, or were intolerant of,
             prior systemic therapy.

          -  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: Arm A,B,C: 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

Last Updated

July 28, 2020