|The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Neoadjuvant CMP-001 plus nivolumab was well tolerated and demonstrated antitumor activity among patients with stage III melanoma, according to the results of a phase 2 study presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).
“Stage III melanoma is a very, very high-risk disease, even despite appropriate management … a large number of patients still relapse. Therefore, the idea behind this is to utilize neoadjuvant approaches to try to get better outcomes,” Diwakar Davar, MD, of the UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania, and presenter of the study, said.
The purpose of this study was to evaluate the effect of intratumoral CMP-001, a type A CpG that activates plasmacytoid dendritic cells (pDCs) and stimulates interferon-alpha production, in combination with nivolumab as a neoadjuvant treatment in high-risk melanoma.
The phase 2 trial treated 31 patients with stage III B/C/D melanoma with CMP-001 plus nivolumab prior to and after surgery. The primary endpoint was major pathologic response (MPR), and secondary endpoints included relapse-free survival (RFS) and overall survival (OS).
At baseline, the median age of patients was 61 years, and 45% of patients were female. The majority of patients had stage IIB disease (57%), followed by 37% who had stage IIIC and 6% who had stage IIID disease. A BRAF mutation was present in 17% of patients. There were 5% of patients previously exposed to ipilimumab and 5% to BRAF/MEK inhibition.
Among 30 evaluable patients, the MPR was 60% and the pathological response was 70%. A complete response was achieved by 50% of patients.
“Responders had a dramatic difference in the CD8 T-cell density post treatment compared with nonresponders … which was almost 10-fold,” Dr Devar said. Nonresponders had similar CD8 T cell density before and after treatment. Peripheral CD8-positive T cells were also upregulated among responders, whereas Tim-3 was upregulated in nonresponders.
The median RFS was not yet reached. RFS was longer among patients who achieved a pathologic response compared with patients whose disease did not respond (P =.0001). The 1-year RFS was 89% among patients who achieved a MPR and 90% among patients who achieved a pathologic response.
There were no dose-limiting toxicities or grade 4 to 5 treatment-related adverse events (TRAEs) reported. There were no delays in surgery due to TRAEs. Grade 3 TRAEs occurred in 26% of patients, with the most common including hypertension, arthralgia/myalgia, colitis, hypophosphatemia, and injection site infection.
Dr Devar concluded that neoadjuvant CMP and nivolumab produced “compelling evidence of immune activation both peripherally and intratumorally, with clear — to my knowledge, the first time — evidence of intratumoral pDCs within the tumor microenvironment in responders.”
Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.
Davar D, Karunamurthy A, Hartman D, et al. Phase II trial of neoadjuvant nivolumab (Nivo) and intratumoral (IT) CMP-001 in high-risk resectable melanoma (Neo-C-Nivo): final results. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 303. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.