Abstract 1885P
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
| A (n=15) | B (n=16) | C (n=30) | D (n=28) | |
| IT | IV | |||
| ORR (95% CI)-% | 13.3 (1.7-40.5) | 12.5 (1.6-38.4) | 23.3 (9.9-42.3) | 17.9 (6.1-36.9) |
| DCR (95% CI)-% | 60.0 (32.3-83.7) | 56.2 (29.9-80.3) | 60.0 (40.6-77.3) | 67.9 (47.7-84.1) |
| PFS median (mo) (80% CI) | 4.3 (3.3-6.3) | 5.6 (2.1-NA) | 4.8 (4.4-8.3) | 6.4 (3.6-12.3) |
| OS median (mo) (80% CI) | 22.0 (22.0-NE) | 20.8 (19.5-NE) | 25.1 (22.7-NE) | 18.5 (14.8-NE) |
| Median duration of response (range,months) | 6.1 (3.7-8.5) | 7.7 (4.1-11.3) | 10.4 (5.5-24.1) | 8.5 (1.1-11.3) |
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.
Resources from the same session
1706P - Time to full approval of novel anticancer medicines granted accelerated approval and implications for reform of the accelerated approval pathway
Presenter: Thomas Hwang
Session: Poster session 23
1707P - Cancer drug prices in the US: Efficacy, innovation, clinical trial evidence, and epidemiology
Presenter: Christoph Michaeli
Session: Poster session 23
1708P - The registration pathways in China for globally developed novel anticancer drugs
Presenter: Da-wei Wu
Session: Poster session 23
1709P - Influence of censoring on conclusions of FDA-approved cancer drugs using the modified time to treatment failure
Presenter: Jonathan Ofer
Session: Poster session 23
1710P - Protocol waivers and consequences on treatment safety and efficacy in the Drug Rediscovery Protocol (DRUP)
Presenter: Laurien Zeverijn
Session: Poster session 23
1711P - The DRUP-like clinical trials family: A distributed European trial network for equitable access to precision medicine
Presenter: Hans Gelderblom
Session: Poster session 23
1712P - Implementation of a molecular pre-screening program (MPP) in a network of public cancer centres for phase I clinical trial (Ph1-CT) candidates: The PREICO program
Presenter: Juan José Soto Castillo
Session: Poster session 23
1713P - Non-inferiority oncology clinical trials in major journals: Purposes, methods and results
Presenter: Rafael Barreto
Session: Poster session 23
1714P - Geographical disparities in access to cancer clinical trials in Korea
Presenter: Sokbom Kang
Session: Poster session 23
1715P - Analysis of the adequacy of control arms in oncology randomized clinical trials published between 2017 and 2021: A meta-research study
Presenter: Alessandro Rossi
Session: Poster session 23