SillaJen Submits CSR to the US FDA for REN026 Study in Patients with RCC

Rhea-AI Summary

SillaJen submits CSR to the US FDA for REN026, a study on Pexa-Vec and cemiplimab in RCC patients. The study shows positive safety and efficacy results, with high response rates and overall survival. Collaboration with Regeneron Pharmaceuticals yields promising outcomes.

Insights

Medical Research Analyst

The recent submission of a Clinical Study Report (CSR) by SillaJen, Inc. for the combination therapy of Pexa-Vec and cemiplimab in renal cell carcinoma (RCC) patients presents promising developments in cancer treatment. The safety profile and efficacy data are pivotal, as they indicate potential advancement in therapeutic options for RCC, which is a hard-to-treat cancer with limited effective treatments, especially for metastatic or unresectable cases.

The reported overall response rate (ORR) and median overall survival (OS) in treatment-naïve patients (Arm C) are significant metrics. ORR serves as a direct indicator of the therapy's ability to shrink tumors, which can be a proxy for clinical benefit. The OS, on the other hand, is a critical endpoint in cancer trials, reflecting the ultimate benefit to patients. The data suggests a comparative advantage over existing therapies, which could translate into a competitive edge in the market. However, it's essential to consider the trial's phase; these results are preliminary and need to be confirmed in larger, phase 3 trials to draw definitive conclusions.

Oncologist

The use of oncolytic viruses like Pexa-Vec, designed to selectively infect and kill cancer cells, in combination with immune checkpoint inhibitors such as cemiplimab, represents an innovative approach to cancer immunotherapy. The mechanism of action involves the oncolytic virus inducing an immune response against the tumor, while the checkpoint inhibitor enhances the immune system's ability to attack cancer cells. The observed efficacy in patients with prior immune checkpoint inhibitor treatments (Arm D) is particularly noteworthy. It suggests that this combination could overcome resistance to previous treatments, a common challenge in advanced cancers.

For patients, especially those with multiple prior systemic regimens, the improvement in ORR and OS is a beacon of hope. It's important to note that these patients often have a poorer prognosis, making any increase in survival rates more valuable. The potential impact on patient care is substantial, offering a new line of therapy where options are currently limited.

Market Research Analyst

From a market perspective, SillaJen's collaboration with Regeneron and the positive study results could have favorable implications for both companies. The oncology market is highly competitive, with significant rewards for therapies that offer improved outcomes. Should Pexa-Vec and cemiplimab receive FDA approval, they could capture a notable share of the RCC treatment market, particularly for patients who have exhausted other treatment options.

The data from this study could also impact Regeneron's stock, as it highlights the potential of cemiplimab in combination therapies. Investors often look for such synergies as indicators of a drug's versatility and market longevity. However, the long-term financial impact will depend on the outcomes of subsequent trials, regulatory approvals and market acceptance. It's also important to monitor how these developments compare with emerging treatments from competitors.

SEOUL, South Korea--(BUSINESS WIRE)-- SillaJen, Inc. (KOSDAQ: 215600) has submitted CSR to the US FDA on 06 Feb 2024 for REN026, a phase 1b/2a dose escalation and safety/efficacy evaluation study of Pexa-Vec in combination with cemiplimab in patients with metastatic or unresectable renal cell carcinoma (RCC).

The study demonstrated an acceptable safety profile and encouraging efficacy of the combination therapy of Pexa-Vec, an engineered oncolytic vaccinia virus, and Libtayo (cemiplimab), anti-PD-1 monoclonal antibody developed by Regeneron Pharmaceuticals Inc. (NASDAQ: REGN).

In 2017, SillaJen began a collaboration agreement with Regeneron for the clinical study of Pexa-Vec in combination with cemiplimab in patients with RCC.

Following the U.S. FDA IND approval in November 2017, SillaJen initiated the trial and 95 patients were enrolled from total of 21 clinical sites in the U.S., South Korea, and Australia. The study ended in February 2023.

The study was conducted in four study arms (A to D) to assess the safety and efficacy of the Pexa-Vec in combination with cemiplimab.

In Arm C, consisting of patients naïve to Immune checkpoint inhibitors (ICIs), Pexa-Vec in combination with cemiplimab showed the overall response rate (ORR) of 23.3% and the median overall survival (OS) of 25.13 months. Both ORR and OS were the highest compared to other study arms.

In Arm D, patients with prior ICI treatment demonstrated ORR of 17.9 %, the second highest of the four arms.

In particular, Arm D included 22 out of 28 patients (78.57%) with the three or more prior systemic regimens in metastatic setting and 5 patients (17.86%) with two prior treatments. Given the typically lower response rates in patients with more prior extensive treatments, the results are considered highly encouraging.

About REN026

1) 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, anti-PD-1monoclonal antibody, in patients with metastatic or unresectable renal cell carcinoma (RCC).

2) Methods
The study enrolled 95 patients in total, including 6 patients in dose-escalation phase and 89 patients with measurable histologically or cytologically confirmed metastatic or unresectable RCC were randomly assigned to one of four study arms.

Patients naïve to immune checkpoint inhibitors (ICIs) with accessible tumors were randomized into Arm A (IT PV and cemiplimab) or Arm B (cemiplimab monotherapy, addition of IT PV upon disease progression).

Patients naïve to ICIs with non-accessible tumors were placed in Arm C with IV PV and cemiplimab, and those with prior ICIs treatment were assigned to Arm D with IV PV and cemiplimab.

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 study arms) was administered every 3 weeks, at a dose of 350 mg.

3) Results
Between June 2018 and February 2023, 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 overall response rate (by RECIST 1.1) across the arms were as follows: Arm A – 13.3% (2PR), Arm B – 12.5% (2 PR), Arm C – 23.3% (1 CR, 6 PR) and Arm D – 17.9% (5 PR).

Median progression-free survival and overall survival for the arms were 4.27/22.0 months, 5.65/20.8 months, 4.57/25.1 months and 6.31/18.5 months, respectively.

All patients experienced treatment-related AEs (any grade); 40 (45.5 %) experienced a grade 3 or 4 event.

Pyrexia was the most common treatment-related AE.

No Grade 5 events occurred in any of the study arms.

4) Summary of efficacy results

	A (n=15)	B (n=16)	C (n=30)	D (n=28)
ORR (95% CI)-%	13.3 (1.7-40.5)	12.5 (1.6-38.3)	23.3 (9.9-42.3)	17.9 (6.06-36.9)
DCR (95% CI)-%	60.0 (32.3-83.7)	56.3 (29.9-80.2)	63.3 (43.9-80.1)	67.9 (47.6-84.1)
PFS median (mo) (80% CI)	4.27 (2.37-NR)	5.65 (2.07-NR)	4.57 (4.34-15.44)	6.31 (3.29-NR)
OS median (mo) (80% CI)	21.98 (21.98-NR)	20.83 (19.52-NR)	25.13 (22.01-NR)	18.53 (14.75-NR)

5) Conclusions
The combination of IV Pexa-Vec 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.

About Pexa-Vec and the SOLVE Platform

Pexa-Vec is SillaJen’s representative investigational product from the company’s proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. 595 cancer patients have been treated with Pexa-Vec as of 31 March, 2023, in multinational clinical trials. Pexa-Vec is engineered to target common genetic defects in cancer cells by deleting its thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration.

About SillaJen

SillaJen, Inc. (KOSDAQ: 215600) is a publicly held biotech company developing anti-cancer therapies, with its clinical-stage products, Pexa-Vec, an oncolytic viral immunotherapy, and BAL0891, a mitotic checkpoint inhibitor. The company is also developing a unique CD-55 expressing vaccinia virus platform, GEEV®, which can be delivered to tumors via intravenous injection while evading the complement system and neutralizing antibodies against oncolytic viruses. Additional information about SillaJen is available at www.sillajen.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240327409454/en/

Investment Relations

Jeong Seok Lee

+82-2-368-2638

js1026@kr.sillajen.com

Public Relations

Jihwan Park

+82-2-368-2643

jayp@kr.sillajen.com

Source: SillaJen, Inc.

FAQ

What study did SillaJen submit to the US FDA?

SillaJen submitted CSR for REN026, a phase 1b/2a study on Pexa-Vec and cemiplimab in RCC patients.

What were the results of the study in Arm C?

In Arm C, Pexa-Vec with cemiplimab showed an ORR of 23.3% and a median OS of 25.13 months, the highest among the study arms.

What collaboration agreement did SillaJen have with Regeneron Pharmaceuticals?

SillaJen collaborated with Regeneron for the clinical study of Pexa-Vec and cemiplimab in RCC patients.

How many patients were enrolled in the study?

A total of 95 patients were enrolled from 21 clinical sites in the U.S., South Korea, and Australia.

What was the response rate in Arm D?

In Arm D, patients with prior ICI treatment showed an ORR of 17.9%, the second highest among the study arms.