Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1

被引:26
作者
Besse, B. [1 ]
Felip, E. [2 ,3 ]
Campelo, R. Garcia [4 ]
Cobo, M. [5 ]
Mascaux, C. [6 ]
Madroszyk, A. [7 ]
Cappuzzo, F. [8 ]
Hilgers, W. [9 ]
Romano, G. [10 ]
Denis, F. [11 ]
Viteri, S. [12 ]
Debieuvre, D. [13 ]
Galetta, D. [14 ]
Baldini, E. [15 ]
Razaq, M. [16 ]
Robinet, G. [17 ]
Maio, M. [18 ,19 ]
Delmonte, A. [20 ]
Roch, B. [21 ]
Masson, P. [22 ]
Schuette, W. [23 ]
Zer, A. [24 ]
Remon, J. [1 ]
Costantini, D. [25 ]
Vasseur, B. [25 ]
Dziadziuszko, R. [26 ,27 ]
机构
[1] Paris Saclay Univ, Inst Gustave Roussy, Canc Med Dept, Villejuif, France
[2] Vall dHebron Univ Hosp, Oncol Dept, Barcelona, Spain
[3] Vall dHebron Inst Oncol, Barcelona, Spain
[4] Complejo Hosp Univ A Coruna, Biomed Res Inst, Med Oncol Dept, INIBIC, La Coruna, Spain
[5] IBIMA, Med Oncol Interctr Unit, Reg & Virgen Victoria Univ Hosp, Malaga, Spain
[6] Hop Univ Strasbourg, Nouvel Hop Civil, Pneumol Dept, Strasbourg, France
[7] IPC Inst Paoli Calmettes, Med Oncol Dept, Marseille, France
[8] IRCCS Regina Elena Natl Canc Inst, Oncol Dept, Rome, Italy
[9] St Catherine Canc Ctr, Med Oncol Dept, Avignon, France
[10] Osped Vito Fazzi ASL Lecce, Med Oncol Dept, Lecce, Italy
[11] Inst Interreg Cancerol Jean Bernard Elsan, Med Oncol Dept, Le Mans, France
[12] Hosp Univ Dexeus, Med Oncol Dept, Inst Oncol Dr Rosell, Grp Quironsalud, Barcelona, Spain
[13] Grp Hosp Reg Mulhouse Sud Alsace, Pneumol Dept, Mulhouse, France
[14] IRCCS Ist Tumori Giovanni Paolo II, Med Thorac Oncol Unit, Bari, Italy
[15] Osped San Luca, Oncol Dept, Lucca, Italy
[16] Stephenson Canc Ctr, Oncol Dept, Oklahoma City, OK USA
[17] Ctr Hosp Reg Univ Morvan, Oncol Dept, Brest, France
[18] Univ Siena, Dept Oncol, Siena, Italy
[19] Univ Hosp, Ctr Immunooncol, Siena, Italy
[20] IRCCS Ist Romagnolo Studio Tumori Dino Amadori IR, Thorac Dept, Meldola, Italy
[21] Montpellier Univ, Univ Hosp Montpellier, Thorac Oncol Unit, Montpellier, France
[22] Ctr Hosp Cholet, Pneumol Dept, Cholet, France
[23] Hosp Martha Maria Halle Doelau, Med Oncol Dept, Halle, Germany
[24] Rabin Med Ctr, Davidoff Canc Ctr, Thorac Canc Serv, Petah Tiqwa, Israel
[25] OSE Immunotherapeut, Med Dev Dept, Paris, France
[26] Med Univ Gdansk, Oncol & Radiotherapy Dept, Gdansk, Poland
[27] Med Univ Gdansk, Early Phase Clin Trials Ctr, Gdansk, Poland
[28] Weill Cornell Med, Meyer Canc Ctr, New York, NY USA
关键词
cancer vaccine; advanced NSCLC; immunotherapy resistance; quality of life; PHASE-II TRIAL; ACQUIRED-RESISTANCE; PATIENTS PTS; DOCETAXEL; ATEZOLIZUMAB; NIVOLUMAB; SURVIVAL;
D O I
10.1016/j.annonc.2023.07.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. Patients and methods: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line >12 weeks. Results: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade >3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). Conclusions: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.
引用
收藏
页码:920 / 933
页数:14
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