1885P - Pexa-vec (thymidine kinase-deactivated vaccinia virus plus GM-CSF) in combination with cemiplimab (REGN2810; ANTI-PD-1) for metastatic or unresectable renal cell carcinoma REN026: Results from a phase II study

Background

Pexa-vec (PV) is an oncolytic and immunotherapeutic vaccinia virus engineered to express GM-CSF. The REN026 study assessed the antitumor activity and safety of intravenous (IV) or intratumoral(IT) PV in combination with cemiplimab (REGN2810, anti-PD-1 inhibitor) in patients with metastatic or unresectable renal cell carcinoma (RCC).

Methods

The study enrolled 89 patients with measurable histologically or cytologically confirmed metastatic or unresectable RCC, randomly assigned to one of four study arms. Patients who were treatment-naive to immune check point inhibitors (ICIs) with accessible tumors were randomized into Arm A (IT PV and cemiplimab) or Arm B (cemiplimab monotherapy, upon disease progression PV (IT) was added. Patients who were treatment-naïve to ICIs with non-accessible tumors were assigned to Arm C with IV PV, and those with prior treatment with ICIs were assigned to Arm D with IV PV. PV was given IT (Arms A and B) administered every 2 weeks or IV (Arms C and D) weekly for 3 or 4 treatments as 1× 10⁹ pfu. Cemiplimab IV infusion (all arms) was administered every 3 weeks, at a dose of 350 mg.

Results

Between June 2018 and October 2022, 89 patients were assigned to the study arms as follows: 15 in Arm A, 16 in Arm B, 30 in Arm C, and 28 in Arm D. The median number of prior systemic regimens in the metastatic setting was 1 (0-4) in Arms A, B, and C and 3 (1-5) in Arm D. With the median follow-up of 22.2 months, efficacy outcomes are shown in table. The most common treatment-related adverse event was pyrexia, with a Grade ≥ 3 of 13.3% in Arm A, 0% in Arm B,0% in Arm C, and 3.6% in Arm D. No Grade 5 events occurred in any of the study arms. Table: 1885P

Summary of efficacy results

Conclusions

The combination immunotherapy of IV PV and cemiplimab demonstrated an acceptable safety profile and encouraging efficacy of ORR and survival with durable responses in patients with metastatic or unresectable RCC, regardless of previous ICI treatment.

Clinical trial identification

NCT03294083.

Editorial acknowledgement

Acknowledgments: None

Legal entity responsible for the study

SillaJen Inc.

Funding

SillaJen Inc

Disclosure

All authors have declared no conflicts of interest.