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

SillaJen

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Renal Cell Carcinoma

Treatments

Biological: Cemiplimab

Biological: Pexastimogene Devacirepvec (Pexa-Vec)

Study type

Interventional

Funder types

Industry

Identifiers

NCT03294083

JX594-REN026

Details and patient eligibility

About

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.

Enrollment

89 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

89 participants in 5 patient groups

Part 1, Dose escalation

Experimental group

Description:

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.

Treatment:

Biological: Pexastimogene Devacirepvec (Pexa-Vec)

Biological: Cemiplimab

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

Experimental group

Description:

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.

Treatment:

Biological: Pexastimogene Devacirepvec (Pexa-Vec)

Biological: Cemiplimab

Part 2-Arm B, Cemiplimab

Experimental group

Description:

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.

Treatment:

Biological: Pexastimogene Devacirepvec (Pexa-Vec)

Biological: Cemiplimab

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

Experimental group

Description:

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

Treatment:

Biological: Pexastimogene Devacirepvec (Pexa-Vec)

Biological: Cemiplimab

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

Experimental group