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

Renal Cell Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03294083
• Other study ID #: JX594-REN026
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 7, 2018
• Est. completion date: November 2023

Study information

• Verified date: August 2022
• Source: SillaJen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 89
• Est. completion date: November 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma
• Vaccinia

Intervention

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

Locations

Country	Name	City	State
Australia	Site 2632 Flinders Medical Centre	Bedford Park
Korea, Republic of	Site 2612 Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Site 2616 Chungnam National University Hospital	Daejeon
Korea, Republic of	Site 2618 Chonnam National University Hwasun Hospital	Gwangju
Korea, Republic of	Site 2622 Gachon University Gil Medical Center	Incheon
Korea, Republic of	Site 2613 Dong-A University Hospital	Pusan
Korea, Republic of	Site 2619 Pusan National University Hospital	Pusan
Korea, Republic of	Site 2617 CHA University, CHA Bundang Medical Center	Seongnam
Korea, Republic of	Site 2620 Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Site 2610 Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Site 2615 Korea University Anam Hospital	Seoul
Korea, Republic of	Site 2623 Ajou University Hospital	Suwon
Korea, Republic of	Site 2625 Wonju Severance Christian Hospital	Wonju
Korea, Republic of	Site 2624 Pusan National University Yangsan Hospital	Yangsan
United States	Site 2646 The Ohio State University	Columbus	Ohio
United States	Site 2644 University of California, Irvine	Irvine	California
United States	Site 2641 University of Miami	Miami	Florida
United States	Site 2643 Washington University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
SillaJen, Inc.	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of, 

Outcome

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