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

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)

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.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Detailed Description

For Pexa-Vec IV infusions (Part 1 / Part 2: Arm C and Arm D): Day -7, 1, 8, and 15), patients allocated to Part 1 or Part 2: Arm C or Arm D will receive an IV infusion of Pexa-Vec in approximately 250 mL buffered saline.

For Pexa-Vec IT Injections (Part 2 Arm A + Arm B), patients in Part 2, Arm A (and those in Arm B who progress on Cemiplimab monotherapy) will receive an IT injection of Pexa-Vec in a volume of buffered saline dependent on size of tumor(s).

For administration of Cemiplimab, Cemiplimab will be administered at a dose of 350 mg IV infusion over 30 minutes (±10 minutes) every 3 weeks per manufactures guidelines.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, SA5042
    • Site 2632 Flinders Medical Centre
  • Camperdown, Australia
    • Site 2631
• South Korea
  • Daegu, South Korea, 41404
    • Site 2612 Kyungpook National University Chilgok Hospital
  • Daejeon, South Korea, 35015
    • Site 2616 Chungnam National University Hospital
  • Gwangju, South Korea, 58128
    • Site 2618 Chonnam National University Hwasun Hospital
  • Incheon, South Korea
    • Site 2622 Gachon University Gil Medical Center
  • Jinju, South Korea, 52727
    • Site 2614 Gyeongsang National University Hospital
  • Pusan, South Korea, 49201
    • Site 2613 Dong-A University Hospital
  • Pusan, South Korea, 49241
    • Site 2619 Pusan National University Hospital
  • Seongnam, South Korea, 35015
    • Site 2617 CHA University, CHA Bundang Medical Center
  • Seongnam-si, South Korea, 13620
    • Site 2620 Seoul National University Bundang Hospital
  • Seoul, South Korea, 02841
    • Site 2615 Korea University Anam Hospital
  • Seoul, South Korea, 03722
    • Site 2610 Severance Hospital, Yonsei University Health System
  • Suwon, South Korea, 16499
    • Site 2623 Ajou University Hospital
  • Wŏnju, South Korea, 50612
    • Site 2625 Wonju Severance Christian Hospital
  • Yangsan, South Korea, 50612
    • Site 2624 Pusan National University Yangsan Hospital
• United States
  • California
    • Irvine, California, United States, 92868
      • Site 2644 University of California, Irvine
  • Florida
    • Miami, Florida, United States, 33136
      • Site 2641 University of Miami
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Site 2643 Washington University
  • Montana
    • Billings, Montana, United States, 59101
      • Site 2642 Billings Clinic
  • Ohio
    • Columbus, Ohio, United States, 43201
      • Site 2646 The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 v1.1. 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 v1.1 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Dose escalation 3 x 10^8 pfu; 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 3 x 10^8 pfu. Cemiplimab will be administered via IV infusion every 3 weeks.	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Experimental: Part 1, Dose escalation 1 x 10^9 pfu; Pexa-Vec will be administered via IV infusion at a dose of 1 x 10^9 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.	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Experimental: Part 2-Arm A, 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. 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 Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Experimental: Part 2-Arm B, 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. 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 Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Experimental: Part 2-Arm C, 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. 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 Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Experimental: Part 2-Arm D, 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. 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 Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)	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 Names: JX-594; Biological: Cemiplimab; Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With Adverse Events From Pexa-Vec Administered by IV Infusions or IT Injections in Combination With IV Cemiplimab	Safety will be determined by assessing the incidence, severity, and frequency of all treatment-emergent adverse events (TEAEs), Grade 3 or greater AEs, serious adverse events (SAEs), laboratory toxicity, AEs requiring discontinuation of study agent(s), and deaths. The severity of all adverse events and laboratory abnormalities is assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Safety is monitored from the first dose throughout the treatment period (up to a maximum of 1 year) and up to 28 days after the last dose of study treatment.	Through study completion without survival follow-up period, an average of 1 year
Overall Response Rate	Overall response rate (ORR) is defined as the proportion of patients whose best overall responses either complete response (CR) or partial response (PR). The best overall response is the best response recorded from the randomization until disease progression. Proportions of patients with a best overall response of CR, disappearance of all target tumors; or PR, at least 30% decrease in the sum of longest diameter of target tumors will be presented by treatment arm along with exact 95% CIs. Analyses will be performed based on central assessments using RECIST v1.1.	Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months.
Number of Participants With Dose Limiting Toxicities of Pexa-Vec Administered by IV Infusions in Combination With Cemiplimab (Part 1 Only)	Dose-limiting toxicity (DLT) was assessed to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of Pexa-Vec. Patients were observed for DLTs during the IV treatment phase through Day 29. DLTs are evaluated based on the severity and frequency of adverse events and laboratory abnormalities using NCI CTCAE Version 5.0.	The 29-day cycle of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Defined as the date of the first study treatment to the date of first documented radiographic tumor progression or death due to any cause, whichever occurs first (RECIST v1.1). Progression free survival will be presented descriptively using Kaplan-Meier curves. Summary statistics from the Kaplan-Meier distributions will be determined, including median PFS and 25% and 75% quartiles with corresponding 95% CIs. The proportions of patients.	Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
Disease Control Rate	Defined as the proportion of patients whose best overall response is either complete response (CR), partial response (PR), or stable disease (SD). (RECIST v1.1)	Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
Overall Survival	Overall survival is defined as the time from first study treatment until death from any cause. For patients not known to have died at the time of the analysis, overall survival will be censored on the date they were last known to be alive. If a patient withdraws early, overall survival will not be censored at the date of withdrawal unless this is the date they were last known to be alive. Date of death will be obtained from the death certificate (preferable) or from a written statement from the primary care or attending physician, or from death registry data. Additionally, for censored date, the latest date of (in the following order): End of Treatment visit(EOT) / Last Radiologic Timepoint(LastRTP) / End of Study(EOS) / Last Drug Date(D.LastDrug) / before cutoff date(2023-02-16) is the censored date.	Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months

Collaborators and Investigators

• Sponsor: SillaJen, Inc.
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: SillaJen Inc., SillaJen, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): February 16, 2023
• Study Completion (Actual): February 16, 2023

Study Registration Dates

• First Submitted: September 19, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Renal cell carcinoma; Clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Neoplasms; Carcinoma, Renal Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; cemiplimab
• Other Study ID Numbers: JX594-REN026

Plan for Individual participant data (IPD)

Study Data/Documents

1. Abstract

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No