Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial

Abstract

Randomized trial of DCVAC/OvCa, dendritic cell-based immunotherapy in platinum-sensitive ovarian cancer.• The addition of DCVAC/OvCa to second-line chemotherapy had a favorable safety profile.• DCVAC/OvCa did not improve progression-free survival, but did prolong overall survival by 13.4 months.• DVCAC/OvCa plus chemotherapy enhanced surrogate T-cell activity.

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

“…Chemotherapy such as gemcitabine has been shown to enhance antigen presentation by inducing tumour cell apoptosis in vitro in colon carcinoma cell lines and holds the potential to enhance vaccine-related immunity [ 92 ]. An early clinical trial of platinum-sensitive relapsed OC demonstrated improved OS when combining DCV with gemcitabine and carboplatin compared to chemotherapy alone, with a median OS of 35.5 versus 22.1 months, respectively, as well as presenting a favourable safety profile [ 93 ]. Similarly, cyclophosphamide has been shown to augment DCV effects in OC due to its ability to deplete Treg numbers.…”

“…The robust antigen-presenting ability of DCs has also been co-opted for developing immunotherapy. The ability of DCVs to stimulate the crucial link between innate and adaptive immune systems has translated into improved survival in early OC trials [ 89 , 93 , 94 , 97 ], leading to the first phase III trial of the autologous DCVAC/OvCa vaccine in platinum-sensitive recurrent OC. If improved survival is observed, we may anticipate the first innate immune cell-based immunotherapy to be approved for OC [ 98 ].…”

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

“…These published studies reported results of trials spanning 13 different cancer types, of which the most common were melanoma, 186–189 followed by GBM/glioma, 190–192 prostate cancer, 193 , 194 ovarian cancer, 195 , 196 and pancreatic cancer 197 , 198 ( Figure 1 ). Relative to our previous report in 2019 149 , while the aforementioned tumor types remain well represented, yet we do see a shift from clinical studies focusing on ‘basket trials’ consisting of multiple tumor types, toward specific trials focusing on a particular oncological indication; such that, only two studies enrolled patients with multiple solid tumors, 199 , 200 while another study focused on peritoneal metastases derived from multiple primary malignancies.…”

“…Most of these studies reported the results of clinical trials evaluating autologous DCs pulsed with TAAs or TAA-derived peptides, 188 , 190 , 191 , 193 , 196–199 , 202 , 203 TAA-coding RNAs, 189 , 194 , 204–206 and autologous cancer cell lysates 187 , 192 , 195 , 201 , 207 ( Figure 1 ). This is in line with the ongoing trends in the field, as reported in our previous Trial Watch (February 2019).…”

“…In the above studies, DC vaccination was either assessed as a single adjuvant therapy 187 , 193 , 194 , 196 , 203 , 205 , 206 , 210 (generally following surgery or standard-of-care), or in combination with various conventional anticancer therapies, most often chemotherapeutics 189 , 192 , 195 , 197–199 , 207 , 208 and other standard-of-care regimens 191 , 202 , 204 ( Figure 1 ). Other trials combined DC vaccination with specific immunotherapeutic agents such as ICBs (primarily, anti-PD1 or anti-CTLA4 antibodies) or immunomodulatory monoclonal antibodies (e.g., anti-CD20) 188 , 197 , 199 , 200 , 209 ( Figure 1 ).…”