SCIB1 Plus Nivolumab/Ipilimumab Generates ORR of 85% in Advanced Unresectable Melanoma

First-line treatment with the DNA vaccine SCIB1 in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) elicited an overall response rate (ORR) of 85% in patients with advanced, unresectable melanoma (n = 13), according to data from stage 1 of the phase 2 SCOPE trial (NCT04079166) presented at the 2024 AACR Annual Meeting.

Findings showed that among the 11 responders, 1 patient experienced a confirmed complete response, and 10 patients achieved confirmed partial responses at 19 weeks and beyond. One patient had stable disease, and another patient had progressive disease. Twenty-four patients have now received SCIB1 as part of the study.

“It looks like there is added benefit [with the addition of SCIB1],” Professor Lindy Durrant said in a presentation of the data. “There was really no toxicity associated with SCIB1, and was particularly useful when added to the double checkpoint inhibitors."

Durrant is an immunologist and professor of cancer immunotherapy in the Academic Department of Clinical Oncology at the University of Nottingham, as well as chief scientific officer and chief executive officer of Scancell in the United Kingdom.

SCIB1 encodes a human IgG1 antibody with 3 epitopes from gp100 and 1 from TRP-2. Additionally, sequences encode 2 HLA-A*0201 restricted CD8 epitopes, which are present in 50% to 60% of the overall population. There are also 2 CD4 epitopes: HLA-DR4 restricted and HLA-DR7, -DR53, and -DQ6 restricted.

After preclinical data supported the rationale of combining SCIB1 with checkpoint inhibitors, and efficacy/safety for the vaccine were demonstrated in monotherapy clinical trials, the SCOPE trial was launched to investigate the vaccine in combination with nivolumab/ipilimumab and in combination with pembrolizumab (Keytruda). Data from stage 1 of the Simon 2 Stage study featuring patients treated with SCIB1 plus nivolumab/ipilimumab were presented at the 2024 AACR Annual Meeting.

Eligibility criteria for patients enrolled onto this study included histologically confirmed, unresectable stage III or IV melanoma; no prior systemic therapy for advanced disease, although prior adjuvant treatment was permitted; an ECOG performance status of 0 or 1; at least 1 measurable lesion per RECIST v1.1 criteria; HLA-A2–­positive disease; and positivity of at least one of the following: HLA-DR4, HLA-DR7, HLA-DR53, or HLA-DQ6. Patients were excluded if they had ocular or mucosal melanoma; active central nervous system metastases; and more than a physiological dose of steroids.

The SCOPE trial has 2 cohorts. Cohort 1 is evaluating SCIB1 plus nivolumab and ipilimumab; cohort 2 is investigating SCIB1 plus pembrolizumab; and cohort 3 is evaluating iSCIB1 in combination with nivolumab plus ipilimumab. SCIB1 is delivered utilizing a needle-free device, and all checkpoint inhibitors are being administered in accordance with standard of care. SCIB1 is being given at weeks 0, 4, 13, and 25, then every 12 weeks thereafter, unless a patient requires steroids for the treatment of toxicities related to checkpoint inhibition.

In evaluable patients from cohort 1 (n = 12), enrolled patients were mostly male (n = 9) and were below 65 years of age (n = 9). All patients had stage IV disease, including M1a (n = 4), M1b (n = 2), and M1c (n = 6). Those evaluable for BRAF status had mutated disease (n = 5) or wild-type disease (n = 6).

Furthermore, 5 patients had lactate dehydrogenase above the upper limit of normal. Total tumor burden ranged from 20 mm to 40 mm (n = 4), 41 mm to 80 mm (n = 3), 81 mm to 150 mm (n = 4), and above 150 mm (n = 1). Four patients received prior adjuvant treatment, which included pembrolizumab (n = 2), nivolumab (n = 1), and dabrafenib (Tafinlar) plus trametinib (Mekinist; n = 1).

Additional data showed that 64% of patients (n = 9/13) experienced detectable T-cell responses per ELISpot.

The SCOPE trial is in its second stage, with 27 of 43 total patients now enrolled. Recruitment is expected to conclude in the second quarter of 2024, and additional data are expected in the fourth quarter of 2024.

Editor’s Note: Dr Durrant is an employee, shareholder, and board member of Scancell.

Reference

Shaw H, Patel P, Payne M, et al. A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma: Efficacy and safety results from the open-label phase 2 SCOPE trial. Presented at: 2024 AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract CT024.