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

NCT03294083 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: JX594-REN026
• Study Type: interventional
• Target: 89
• Locations: 3 countries
• Sites: 18

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.

Conditions

Renal Cell Carcinoma

Keywords

Cancer; Renal cell carcinoma; Clear cell renal cell carcinoma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)

  MTD/MFD of Pexa-Vec administered by IV infusion in combination with Cemiplimab

  36 days after first treatment

• Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab

  Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03

  From date of first treatment until 28 days after last treatment

• Overall response rate

  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)

  Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months

Secondary Outcomes (4)

• Progression free survival

  Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months

• Disease control rate

  Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months

• Best radiographic response

  Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months

• Overall survival

  Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months

Study Arms (5)

Part 1, Dose escalation

EXPERIMENTAL

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.

Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab

EXPERIMENTAL

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.

Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Part 2-Arm B, Cemiplimab

EXPERIMENTAL

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.

Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab

EXPERIMENTAL

Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks.

Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab

EXPERIMENTAL

Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks.

Biological: Pexastimogene Devacirepvec (Pexa-Vec); Biological: Cemiplimab

Interventions

Pexastimogene Devacirepvec (Pexa-Vec) BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Also known as: JX-594

Part 1, Dose escalation; Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab; Part 2-Arm B, Cemiplimab; Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab; Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab

Cemiplimab BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Part 1, Dose escalation; Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab; Part 2-Arm B, Cemiplimab; Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab; Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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).
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SillaJen, Inc.: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (18)

Site 2644 University of California, Irvine

Irvine, California, 92868, United States

Location

Site 2641 University of Miami

Miami, Florida, 33136, United States

Location

Site 2643 Washington University

St Louis, Missouri, 63141, United States

Location

Site 2646 The Ohio State University

Columbus, Ohio, 43201, United States

Location

Site 2632 Flinders Medical Centre

Bedford Park, SA5042, Australia

Location

Site 2612 Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Site 2616 Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Site 2618 Chonnam National University Hwasun Hospital

Gwangju, 58128, South Korea

Location

Site 2622 Gachon University Gil Medical Center

Incheon, South Korea

Location

Site 2613 Dong-A University Hospital

Pusan, 49201, South Korea

Location

Site 2619 Pusan National University Hospital

Pusan, 49241, South Korea

Location

Site 2617 CHA University, CHA Bundang Medical Center

Seongnam, 35015, South Korea

Location

Site 2620 Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Site 2615 Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Site 2610 Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Site 2623 Ajou University Hospital

Suwon, 16499, South Korea

Location

Site 2625 Wonju Severance Christian Hospital

Wŏnju, 50612, South Korea

Location

Site 2624 Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 26, 2017
• Study Start: June 7, 2018
• Primary Completion: August 1, 2023
• Study Completion: November 1, 2023
• Last Updated: October 27, 2022

Record last verified: 2022-08

Locations

US (4); AU (1); KR (13)