Tumor-Directed Oncolytic Immunotherapies Show Promise in Replimune Clinical Update

Vusolimogene oderparepvec (RP1) shows promise as a monotherapy in solid organ transplant recipients with skin cancer, while phase 2 data from completed cohorts in the IGNYTE clinical trial in non-melanoma skin cancer is also showing promise, according to a recent clinical data update from Replimune.

Replimune Group is developing a novel class of tumor-directed oncolytic immunotherapies, according to a press release from the company. In addition to new data from the IGNYTE clinical trial, the company also announced new data from an ongoing clinical trial in anti-programmed cell death protein 1 (PD-1) failed non-melanoma skin cancer (NMSC) and from the ARTACUS clinical trial of RP1.

RP1 is in development for the treatment of multiple skin cancers either alone or in combination with anti-PD1 therapy. In the phase 2 part of the IGNYTE clinical trial, RP1 was combined with nivolumab. Researchers have completed enrollment of the anti-PD1 naïve NMSC cohort that included patients with cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and angiosarcoma. Ongoing efficacy data are available for 31 patients.

According to the researchers, RP1 in combination with nivolumab continues to be generally well tolerated, with no new safety signals identified since the last data cutoff in June 2021. The efficacy data continue to show that RP1 in combination with nivolumab contributes to deep and durable responses across the full range of tumor types enrolled in the trial. Patients have continued to improve since June 2021.

In patients with CSCC, a further complete response has been documented and the overall response rate (ORR) is now 65%, compared to 60% at the June 2021 update. The complete response rate has remained static at 47%. Finally, updated response rates in BCC, MCC, and angiosarcoma were 25%, 75%, and 67%, respectively, with multiple complete responses documented.

According to the press release, these data strongly suggest differentiation versus anti-PD-1 therapy alone and provides strong validation of the current registration-directed clinical trial in CSCC. The primary data readout expected in early 2023.

Researchers also provided updated efficacy data from the IGNYTE trial in both anti-PD-1 failed and anti-PD-1 naïve patients with melanoma who were treated with RP1 combined with nivolumab. In this trial, 36 patients were enrolled and the data show that RP1 combined with nivolumab continues to demonstrate deep and durable responses, which tend to deepen over time.

ORR in anti-PD-1 naïve cutaneous melanoma remains at 62.5%. Sixteen participants had cutaneous melanoma and had previously failed treatment with checkpoint therapy, and have a current ORR of 37.5%, which is an improvement from the 31% ORR reported in June 2021. This includes 2 complete responses.

In the IGNYTE trial cohort with anti-PD(L)-1 failed NMSC patients treated with RP1 and nivolumab, researchers are actively enrolling a 30-patient cohort. As of the date for the initial data cutoff, the ORR in this group was 33.3% with responses observed in anti-PD(L)-1 failed CSCC, MCC, and angiosarcoma, including 1 complete response. Other patients who remain in the study with a shorter follow-up are also showing tumor shrinkage, according to the study.

The clear activity of RP1 combined with nivolumab in anti-PD(L)-1 failed patients represents a new potential therapeutic option for these patients and supports the broad potential for RP1 in skin cancers, including those with anti-PD(L)-1 failed disease, according to the press release.

Finally, investigators also released new safety and efficacy data from the phase 1b/2 ARTACUS trial evaluating RP1 monotherapy in solid organ transplant recipients with CSCC. The ARTACUS trial is a 65-patient clinical trial with potential registrational intent.

Although numbers are small, RP1 monotherapy in solid organ transplant patients has so far demonstrated a similar safety profile to that observed in patients who are not immune suppressed, according to the study. Initial clinical evidence of activity has been seen, with 2 out of 6 patients (33%) achieving response, with 1 complete response and 1 partial response.

“The frequency, depth, and durability of responses seen across a range of skin cancers with RP1 alone and combined with Opdivo, including in anti-PD-1 failed disease, suggests broad utility of the approach,” said Kevin Harrington, PhD, MBBS, MRCP, FRCR, FRCP, DIC, in the press release. “Based on this data, I look forward to seeing the results of the registration-directed studies in CSCC and anti-PD-1 failed melanoma and the potential provision of a new treatment paradigm for these patients.”

REFERENCE

Replimune Provides New Clinical Data, Broad Program Update and Future Development Strategy for its Tumor-Directed Oncolytic Immunotherapies. News release. Replimune; March 30, 2022. Accessed April 13, 2022. https://ir.replimune.com/news-releases/news-release-details/replimune-provides-new-clinical-data-broad-program-update-and