Phase 2 SCOPE Trial of SCIB1 Achieves Positive ORR in Advanced Melanoma

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In patients with advanced melanoma treated with SCIB1 in combination with checkpoint inhibitors (CPIs), there was an 82% objective response rate (ORR) to treatment, according to initial data from the first stage in the phase 2 SCOPE trial (NCT04079166).¹

To date, 11 of 16 study patients have reached 13 weeks and been evaluated at radiological imaging. Nine of these patients have already shown an objective response with no increase in toxicity. These data were better than the 70% ORR that the trial was configured to show, and better than the 50% ORR seen in patients treated with the current standard-of-care alone.

Also at this time, the reduction in tumor volume was 31%-94%. There were 4 patients who reached the 25 weeks imaging evaluation and showed a 69%-94% reduction in total tumor burden, and 2 who reached the 37 weeks who showed an 87%-94% reduction, respectively. This compared with an ORR of 50% in patients receiving this doublet CPI therapy in the real-world setting with a progression-free survival (PFS) time of 11.5 months.

“These results, if confirmed in a larger cohort, will be a significant improvement on what patients can expect from available treatment today. We look forward to continuing the second stage of the study and reporting further data in due course,” said Poulam Patel, PhD, chief investigator, in a press release.

The phase 2, international, multicenter, open-label SCOPE trial plans to determine if the ORR in patients with unresectable metastatic melanoma could be improved when given combination regimens with CPIs. During the first stage of the trial, patients were treated with SCIB1 via a needle-free device plus nivolumab (Opdivo) with pembrolizumab (Keytruda) or ipilimumab (Yervoy).²

Primary end points of the study include safety, tolerability, and ORR. Secondary end points being investigated are duration of response, ORR assessed by modified RECIST v1.1., PFS, overall survival, safety, and tolerability.

Patients aged 18 years and older with a histologically confirmed diagnosis of unresectable Stage III or Stage IV melanoma who have not received prior systemic treatment for advanced disease and those with a BRAF status that is known are eligible for enrollment in the study. At least one measurable lesion per RECIST 1.1 criteria by CT scan or MRI. In addition, patients are required to have a biopsy sample of tumor available for analysis of programmed PD-L1 expression, be HLA-A2 positive, be positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6, have a life expectancy 3 months or more, an ECOG performance status of 0 or 1, and adequate organ function to be enrolled in the study.

In the first part of the SCOPE trial, investigators aimed to have more than 8 of 15 patients achieve responses, which would suggest that SCIB1 in combination with doublet CPI therapy might meaningfully improve current outcomes for these patients. A total of 16 stage IV patients with metastatic disease have received this combination, and outcomes were positive.¹

The SCOPE trial is now entering this second stage and plans to recruit another 27 patients, making for a total of 43 enrolled in the study. The goal of the trial is to achieve at least 27 responses in total, which would show that the combination of SCIB1 with doublet therapy exceeds current ORRs.

Recruitment is expected to be complete by the end of 2023, and data is anticipated to be announced towards the start of 2024. Based upon the first 11 patients there is a greater than 90% probability that the second phase will also be successful.

“We are excited by these highly impressive results for SCIB1 combined with the doublet CPI therapy. We thought results from the phase 1/2 trial evaluating SCIB1 as a monotherapy were positive but results from this combination are even more meaningful. Previous studies indicated that a response rate of 50% was the best that could be achieved in the real world setting for patients with unresectable metastatic melanoma, as no other combination had improved on the response rates for doublet CPI alone. Confirmation of this data in a larger cohort could make a significant impact on melanoma patient survival, especially as melanoma is now one of the most common cancers in young women,” said Lindy Durrant, PhD, chief executive officer of Scancell, in the press release.1

REFERENCES:

1. Scancell announces positive data from the first stage in its phase 2 SCOPE trial with SCIB1 cancer vaccine delivered by needle free injection for advanced melanoma. News release. Scancell Holdings plc. September 19, 2023. Accessed September 20, 2023. https://tinyurl.com/bdepwekc

2. SCIB1 in melanoma patients receiving either nivolumab with ipilimumab or pembrolizumab (The SCOPE study). ClinicalTrials.gov. Updated March 2, 2023. Accessed September 20, 2023. https://tinyurl.com/mwvs36wn