Autologous Dendritic Cell-based Immunotherapy (DCVAC/LuCa) and carboplatin/paclitaxel in Advanced Non-Small Cell Lung Cancer: A randomized, open-label, phase I/II trial

Eligibility criteria

Survival rate

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Summary

The study aims to investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with non-small cell lung cancer (NSCLC). as a result DCVAC/LuCa in combination with carboplatin and paclitaxel extended overall survival (OS) and was well tolerated.

Patients characteristics

Patients were aged ≥18 years with histologically or cytologically confirmed stage IV unresectable NSCLC of adenomatous, squamous, or large cell carcinoma histology. Patients with measurable or non-measurable disease according to RECIST 1.1 criteria. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0–1. The mean age of the patients was 65 years (range: 22–77 years), and 90% of the patients were diagnosed within 3 months prior to randomization. Most patients (93%) were diagnosed with stage IV NSCLC, and half of the patients (47%) had squamous cell carcinoma (because the histologic type was a stratification factor for randomization).

Methodology

Each DCVAC/LuCa dose comprises DCs loaded with antigens derived from the H522 and H520 cell lines. To prepare DCVAC/LuCa, peripheral blood mononuclear cells, obtained via leukapheresis and gradient centrifugation, are first cultured in a medium containing interleukin-4 and granulocyte-macrophage colony-stimulating factor. Immature DCs are separated, co-cultured (pulsed) with HHP-treated H522 and H520 cells, and matured using polyinosinic:polycytidylic acid. The resulting product is cryopreserved at a concentration of approximately 107 DCs in 1 mL of CryoStor CS10 per vial.

Treatment

Patients were divided into three groups in a ratio of 1:1:1 to receive DCVAC/LuCa and chemotherapy (Group A n=40); DCVAC/LuCa, chemotherapy, pegylated IFN- a2b, and hydroxychloroquine (Group B n=29); or chemotherapy alone (Group C n=38)
Within 14 days after randomization, patients in Groups A and B underwent one session of leukapheresis. Patients in Group C did not undergo leukapheresis to avoid unnecessary exposure to medical procedures with their inadvertent risks. Chemotherapy was initiated 2– 5 days after leukapheresis (Groups A and B) or within 2 weeks after randomization (Group C).
All patients received paclitaxel 175 mg/m2 intravenously (IV) over 3 hours followed by carboplatin area under the curve 6 mg/mL per minute intravenously over 15–30 min. Four cycles of chemotherapy were administered to all patients. Patients with stable disease, partial response, or complete response after cycle four could continue chemotherapy for up to six cycles at the investigator’s discretion. Paclitaxel and carboplatin were administered according to theapproved prescribing information. Standard supportive care and dose modifications for paclitaxel and carboplatin were recommended.
Patients in Groups A and B received up to 15 doses of DCVAC/LuCa, starting during the second cycle of chemotherapy. On the day of administration, 1 mL aliquot of DCVAC/LuCa was thawed and diluted with 0.9% saline solution to a total volume of 5 mL. Two 2.5 mL injections were subcutaneously administered into the axillary and contralateral inguinal lymph node areas. DCVAC/LuCa was administered every 3 weeks for the first 5 doses and then every 6 weeks.
Patients in Group B also received pegylated IFN-α2b and hydroxychloroquine. One dose of pegylated IFN-α2b, 1 μg/kg, was divided into two aliquots and subcutaneously administered within a10cm radius from theinjection siteof DCVAC/LuCa after each administration of DCVAC/LuCa. Hydroxychloroquine was administered in two doses of 400 mg orally daily for 7 consecutive days, starting 1 day after each DCVAC/LuCa administration.

Results

The final analysis in the mITT population showed that the median overall survival (OS) was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months). This improvement in OS in favor of the DCVAC/LuCa group was statistically significant (p = 0.0179).
The robustness of the result was also confirmed in the per protocol (PP) population. The median OS was 4.3 months longer in Group A than in Group C (16.4 vs. 12.1 months). This improvement was statistically significant (p = 0.0316).
As of January 2021, six patients in the DCVAC/LuCa groups (4 in Group A and 2 in Group B) were alive; no patients were alive in the control group.
The median PFS in the mITT population was 1.1 months longer in Group A than in Group C (6.7 vs. 5.6 months). This improvement in PFS in favor of the DCVAC/LuCa group was statistically significant (p = 0.0334).

The AE reporting period differed significantly between the treatment groups, with a mean duration of 8.6 months in Groups A and B and 3.9 months in Group C. TEAEs (any), PP therapy- related TEAEs, serious TEAEs, and TEAEs leading to discontinuation of chemotherapy were reported in similar proportions of patients in each group.(Group A vs. B vs. C; any TEAEs: 97.5% vs. 100.0% vs. 97.1%; PP therapy-related TEAEs: 95.0% vs. 96.3% vs. 88.2%; serious TEAEs: 32.5% vs. 48.1% vs. 26.5%; TEAEs leading to discontinuation of chemotherapy: 2.5% vs. 7.4% vs. 2.9%).
Grade 1–2 TEAEs related to DCVAC/LuCa were reported in only 5.0% (2 patients) of patients in Group A and in 14.8% (4 patients) of patients in Group B. No TEAE led to discontinuation of DCVAC/LuCa. Grade 3– 5 TEAEs and TEAEs leading to death were reported in higher proportions
of patients in Groups A and B than in Group C (Group A vs. B vs. C; NCI CTCAE Grade 3–5 TEAEs: 72.5% vs. 70.4% vs. 38.2%; TEAEs leading to death: 22.5% vs. 33.3% vs. 5.9%). Most deaths were caused by progression of the underlying disease in Groups A, B, and C (96.8%, 91.3%, and 93.6%). Disease progression was more frequently reported as a TEAE in Group A than in Group C. However, disease progression leading to death was observed more frequently in Group C. No deaths were reported to be related to DCVAC/LuCa, leukapheresis, or chemotherapy.

Conclusion

In conclusion, Although exploratory in nature, the totality of evidence speaks in favor of the beneficial effect of the addition of DCVAC/LuCa to chemotherapy in patients with stage IV NSCLC resulting in improved OS and PFS compared to that achieved using chemotherapy alone.

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Scientific article publishing date : 26/06/2021

Immucura identifier : BSC21_059EN

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