Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers

R Zhong; X Ling; S Cao; J Xu; B Zhang; X Zhang; H Wang; B Han; H Zhong

doi:10.1016/j.esmoop.2021.100334

Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers

ESMO Open. 2022 Feb;7(1):100334. doi: 10.1016/j.esmoop.2021.100334. Epub 2021 Dec 24.

Authors

R Zhong¹, X Ling¹, S Cao¹, J Xu¹, B Zhang¹, X Zhang¹, H Wang¹, B Han², H Zhong³

Affiliations

¹ Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
² Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. Electronic address: 18930858216@163.com.
³ Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. Electronic address: eddiedong8@hotmail.com.

Abstract

Background: Our prospective, open-label, single-arm phase II study investigated the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with standard carboplatin/pemetrexed in advanced non-squamous (nsq) non-small-cell lung cancer (NSCLC).

Patients and methods: Eligible patients had stage IV nsq NSCLC without oncogenic drivers and had not received prior systemic cancer therapy. Treatment consisted of carboplatin/pemetrexed for up to 6 cycles followed by 21 cycles of pemetrexed maintenance or until progression or intolerance. Non-progression patients after two cycles of chemotherapy started to receive DCVAC/LuCa subcutaneously (s.c.) on day 15 of cycle 3, and thereafter q3w (day 15 of chemotherapy cycles) for up to 15 doses. Dosing of DCVAC/LuCa s.c. varied among patients depending on the baseline number of leucocytes but remained constant for each single patient. Safety was assessed by adverse events (AEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Efficacy was measured by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR).

Results: Sixty-one patients were enrolled. In the safety population (n = 60), eight patients (13.33%) had grade 3 or greater TRAEs, and six patients (10.0%) showed SAEs which were not related to leukapheresis or DC vaccination. Six grade 1 AEs were considered to be related to leukapheresis. No AESIs or DCVAC/LuCa-induced AEs were observed. The 2-year survival rate in the modified intention-to-treat population (n = 44) was 52.57%. Median OS was not reached. Median PFS was 8.0 months, median TTP was 10.2 months, and the ORR was 31.82%.

Conclusion: In treatment-naïve stage IV nsq NSCLC patients without oncogenic drivers, the combination of carboplatin/pemetrexed and DCVAC/LuCa was well tolerated and showed promising efficacy. Therefore, a study to prove our immunotherapeutic concept in a randomized phase III trial is planned.

Keywords: DCVAC/LuCa; dendritic cell vaccination; non-small-cell lung cancer.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / analogs & derivatives
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carboplatin / pharmacology
Carboplatin / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Dendritic Cells
Humans
Immunotherapy / adverse effects
Lung Neoplasms* / drug therapy
Pemetrexed / pharmacology
Pemetrexed / therapeutic use
Prospective Studies

Substances

Pemetrexed
S-1,2-dichlorovinyl-N-acetylcysteine
Carboplatin
Acetylcysteine