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

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ClinicalTrials.gov Identifier: NCT03294083
Recruitment Status : Recruiting
First Posted : September 26, 2017
Last Update Posted : January 19, 2021
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
SillaJen, Inc.

Tracking Information
First Submitted Date  ICMJE September 19, 2017
First Posted Date  ICMJE September 26, 2017
Last Update Posted Date January 19, 2021
Actual Study Start Date  ICMJE June 7, 2018
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
  • Maximum tolerated dose(MTD) / Maximum feasible dose (MFD) [ Time Frame: 36 days after first treatment ]
    MTD/MFD of Pexa-Vec administered by IV infusion in combination with Cemiplimab
  • Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab [ Time Frame: From date of first treatment until 28 days after last treatment ]
    Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03
  • Overall response rate [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
    Evaluate anti-tumor activity and efficacy of IV or IT Pexa-Vec combined with IV Cemiplimab with respect to overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2017)
  • Maximum tolerated dose(MTD) / Maximum feasible dose (MFD) [ Time Frame: 36 days after first treatment ]
    MTD/MFD of Pexa-Vec administered by IV infusion in combination with REGN2810
  • Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV REGN2810 [ Time Frame: From date of first treatment until 28 days after last treatment ]
    Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2017)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2017)
  • Overall response rate [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma
Official Title  ICMJE A Phase 1b/2a Dose-escalation and Safety/Efficacy Evaluation Study of Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) in Combination With Cemiplimab (REGN2810; Anti-PD-1) in Patients With Metastatic or Unresectable Renal Cell Carcinoma (RCC)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Carcinoma
Intervention  ICMJE
  • Biological: Pexastimogene Devacirepvec (Pexa-Vec)
    Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells
    Other Name: JX-594
  • Biological: Cemiplimab
    Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Study Arms  ICMJE
  • Experimental: Part 1, Dose escalation

    Pexa-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.

    Cemiplimab will be administered via IV infusion every 3 weeks.

    Interventions:
    • Biological: Pexastimogene Devacirepvec (Pexa-Vec)
    • Biological: Cemiplimab
  • Experimental: Part 2, Pexa-Vec (IT) and Cemiplimab

    Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments.

    Cemiplimab will be administered via IV infusion every 3 weeks.

    Interventions:
    • Biological: Pexastimogene Devacirepvec (Pexa-Vec)
    • Biological: Cemiplimab
  • Experimental: Part 2, Cemiplimab

    Cemiplimab 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. Cemiplimab will continue every 3 weeks.

    Intervention: Biological: Cemiplimab
  • Experimental: Part 2, Pexa-Vec (IV) and Cemiplimab

    Pexa-Vec will be administered via IV infusion once per week for 4 treatments.

    Cemiplimab will be administered via IV infusion every 3 weeks.

    Interventions:
    • Biological: Pexastimogene Devacirepvec (Pexa-Vec)
    • Biological: Cemiplimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2021)
117
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2017)
89
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 6 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Angelica Craighead (415) 814-9865 patient_inquiry@sillajen.com
Contact: RaHee Kim (415) 238- 4382 rhkim@kr.sillajen.com
Listed Location Countries  ICMJE Australia,   Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03294083
Other Study ID Numbers  ICMJE JX594-REN026
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  ICMJE Not Provided
Responsible Party SillaJen, Inc.
Study Sponsor  ICMJE SillaJen, Inc.
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Kyoung Soo Ha, MD PhD SillaJen Biotherapeutics
PRS Account SillaJen, Inc.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP