Cell concentrates (60 to 150 mL) containing a minimum of 4×109 peripheral blood mononuclear cells (PBMCs) were collected. Within 30 hours after the beginning of leukapheresis, the cells were delivered under controlled conditions to the processing facility, where harvested monocytes were cultured in the presence 500 IU/mL recombinant human colony stimulating factor 2 (GM- CSF) and 248 IU/mL recombinant human interleukin 4 (IL-4) to generate immature DCs (iDCs).
iDCs were then pulsed with human OV-90 and SK-OV-3 ovarian cancer cells pre-treated with high hydrostatic pressure for the induction of immunogenic cell death. DCs loaded with immunogenic tumor cells were subsequently treated with 25 μg/mL poly(I:C), a Toll-like receptor 3 (TLR3) ligand, to induce phenotypic and functional maturation. The DCVAC/OvCa product was cryopreserved at a concentration of approximately 1×107 mature DCs/mL as 1 mL aliquots and stored in liquid nitrogen.
Chemotherapy started 7 days after leukapheresis (DCVAC/OvCa group) or 2 weeks after randomization (control group). All patients received carboplatin and gemcitabine in 21-day cycles. In each cycle, carboplatin (AUC 4–5) was intravenously administered on day 1 and gemcitabine (1000 mg/m2) on days 1 and 8. Patients were scheduled to receive 6, 8, or 10 cycles of chemotherapy according to the investigator’s decision.
Patients in the DCVAC/OvCa group received up to 10 doses of DCVAC/OvCa, starting after the second cycle of chemotherapy. On the day of administration, one 1 mL aliquot of DCVAC/OvCa was thawed and diluted with 0.9% saline to a total volume of 5 mL. Two 2.5 mL injections were administered subcutaneously into the axillary and contralateral inguinal lymph node areas. These regions were chosen based on prior phase 1/2 trials in which administration of DCVAC in close proximity to the axillary and contralateral inguinal lymph nodes resulted in efficient migration of the DCVAC-related DCs to lymph nodes with strong potency to prime the anti-tumor T cell response.
Within the DCVAC/OvCa (n = 37) and control (n = 31) groups, similar proportions experienced TEAEs (97.3% vs 100.0%), chemotherapy- related TEAEs (94.6% vs 100.0%), and grade 3 TEAEs (78.4% vs 83.9%). Fewer patients experienced serious TEAEs or TEAEs leading to discontinuation of chemotherapy in the DCVAC/OvCa group. TEAEs related to DCVAC/OvCa were reported in six patients (16.2%), of which three were only related to DCVAC/OvCa (abdominal rigidity, injection site erythema, and lymphadenopathy). No TEAE led to discontinuation of DCVAC/OvCa.
Thirty-two patients were included in each group for the efficacy analyses, which were performed 72 weeks after the initiation of second-line chemotherapy in the last patient.
Median PFS was 11.3 vs 9.5 months in the DCVAC/OvCa vs control groups and was not significantly different between the two groups (HR 0.73, 95% CI 0.42–1.28, P=0.274). Furthermore, the median PFIBIO was not greater in the DCVAC/OvCa group (10.3 vs 10.1 months: HR 0.82, 95% CI 0.47–1.43, P = 0.478).
The median OS of 23.8 months in the DCVAC/OvCa group vs 21.5 months in the control group (HR 0.63, 95% CI: 0.26–1.54, P = 0.303).
The ORR was greater in the DCVAC/OvCa group (87.5%, 95% CI 71.0–96.5) compared with the control group (62.5%, 95% CI 43.7–78.9).
In conclusion, the data shows that DCVAC/OvCa combined with gemcitabine plus carboplatin as second-line treatment and continued as maintenance therapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but exploratory analyses showed it may have prolonged OS and enhanced surrogate antigen-specific T-cell activity.
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Scientific article publishing date : 19/07/2021
Immucura identifier : BSC21_066EN