Safety and efficacy of dendritic cell-based immunotherapy
DCVAC/OvCa added to first-line chemotherapy (carboplatin plus
paclitaxel) for epithelial ovarian cancer: a phase 2,
open-label, multicenter, randomized trial

J 2022

Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial

ROB, Lukas, David CIBULA, Pawel KNAPP, Peter MALLMANN, Jaroslav KLAT et. al.

Basic information

Original name

Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial

Authors

ROB, Lukas (203 Czech Republic), David CIBULA (203 Czech Republic), Pawel KNAPP, Peter MALLMANN, Jaroslav KLAT (203 Czech Republic), Luboš MINÁŘ (203 Czech Republic, belonging to the institution), Pavel BARTOS (203 Czech Republic), Josef CHOVANEC (203 Czech Republic), Petr VALHA (203 Czech Republic), Marek PLUTA (203 Czech Republic), Zdenek NOVOTNY (203 Czech Republic), Jiri SPACEK (203 Czech Republic), Bohuslav MELICHAR (203 Czech Republic), Dariusz KIESZKO (203 Czech Republic), Jitka FUCIKOVA (203 Czech Republic), Tereza HRNCIAROVA (203 Czech Republic), Roman Pawel KOROLKIEWICZ, Marek HRASKA (203 Czech Republic, guarantor), Jirina BARTUNKOVA (203 Czech Republic) and Radek SPISEK (203 Czech Republic)

Edition

Journal for ImmunoTherapy of Cancer, Switzerland, Springer International Publishing AG, 2022, 2051-1426

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.900

RIV identification code

RIV/00216224:14110/22:00125193

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1136/jitc-2021-003190

UT WoS

000740755400004

Keywords in English

immunotherapy; clinical trials; phase II as topic; dendritic cells

Abstract

V originále

Background Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2. Methods Patients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients' CD14(+) monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1. Results Between November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events). Conclusions DCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC.

Citovat

ROB, Lukas, David CIBULA, Pawel KNAPP, Peter MALLMANN, Jaroslav KLAT, Luboš MINÁŘ, Pavel BARTOS, Josef CHOVANEC, Petr VALHA, Marek PLUTA, Zdenek NOVOTNY, Jiri SPACEK, Bohuslav MELICHAR, Dariusz KIESZKO, Jitka FUCIKOVA, Tereza HRNCIAROVA, Roman Pawel KOROLKIEWICZ, Marek HRASKA, Jirina BARTUNKOVA and Radek SPISEK. Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial. Journal for ImmunoTherapy of Cancer. Switzerland: Springer International Publishing AG, 2022, vol. 10, No 1, p. 1-11. ISSN 2051-1426. Available from: https://dx.doi.org/10.1136/jitc-2021-003190.

@article{1823831,
   author = {Rob, Lukas and Cibula, David and Knapp, Pawel and Mallmann, Peter and Klat, Jaroslav and Minář, Luboš and Bartos, Pavel and Chovanec, Josef and Valha, Petr and Pluta, Marek and Novotny, Zdenek and Spacek, Jiri and Melichar, Bohuslav and Kieszko, Dariusz and Fucikova, Jitka and Hrnciarova, Tereza and Korolkiewicz, Roman Pawel and Hraska, Marek and Bartunkova, Jirina and Spisek, Radek},
   article_location = {Switzerland},
   article_number = {1},
   doi = {http://dx.doi.org/10.1136/jitc-2021-003190},
   keywords = {immunotherapy; clinical trials; phase II as topic; dendritic cells},
   language = {eng},
   issn = {2051-1426},
   journal = {Journal for ImmunoTherapy of Cancer},
   title = {Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial},
   url = {https://jitc.bmj.com/content/10/1/e003190},
   volume = {10},
   year = {2022}
}

TY  - JOUR
ID  - 1823831
AU  - Rob, Lukas - Cibula, David - Knapp, Pawel - Mallmann, Peter - Klat, Jaroslav - Minář, Luboš - Bartos, Pavel - Chovanec, Josef - Valha, Petr - Pluta, Marek - Novotny, Zdenek - Spacek, Jiri - Melichar, Bohuslav - Kieszko, Dariusz - Fucikova, Jitka - Hrnciarova, Tereza - Korolkiewicz, Roman Pawel - Hraska, Marek - Bartunkova, Jirina - Spisek, Radek
PY  - 2022
TI  - Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial
JF  - Journal for ImmunoTherapy of Cancer
VL  - 10
IS  - 1
SP  - 1-11
EP  - 1-11
PB  - Springer International Publishing AG
SN  - 20511426
KW  - immunotherapy
KW  - clinical trials
KW  - phase II as topic
KW  - dendritic cells
UR  - https://jitc.bmj.com/content/10/1/e003190
N2  - Background Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2. Methods Patients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients' CD14(+) monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1. Results Between November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events). Conclusions DCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC.
ER  -

ROB, Lukas, David CIBULA, Pawel KNAPP, Peter MALLMANN, Jaroslav KLAT, Luboš MINÁŘ, Pavel BARTOS, Josef CHOVANEC, Petr VALHA, Marek PLUTA, Zdenek NOVOTNY, Jiri SPACEK, Bohuslav MELICHAR, Dariusz KIESZKO, Jitka FUCIKOVA, Tereza HRNCIAROVA, Roman Pawel KOROLKIEWICZ, Marek HRASKA, Jirina BARTUNKOVA and Radek SPISEK. Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial. \textit{Journal for ImmunoTherapy of Cancer}. Switzerland: Springer International Publishing AG, 2022, vol.~10, No~1, p.~1-11. ISSN~2051-1426. Available from: https://dx.doi.org/10.1136/jitc-2021-003190.

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