FASTing-like Approach and Maintenance IMMunotherapy in ES-SCLC Patients Not Progressing on Chemoimmunotherapy Induction

Summary

Cyclic, 5-day calorie restriction is a safe metabolic intervention when combined with standard therapies in cancer patients, favorably reshaping peripheral blood and intratumor metabolism and immunity in a way that may improve the antitumor activity and efficacy of immunotherapy. The goal of this clinical trial is to test if combining cyclic, 5-day calorie restriction with atezolizumab maintenance in patients with ES SCLC achieving at least stable disease after four cycles of induction atezolizumab plus carboplatin and etoposide chemoimmunotherapy may increase the efficacy of a standard first-line, chemo-immunotherapy approach in terms of patient PFS. The main question it aims to answer is: • does the combination of cyclic, 5-day calorie restriction with triweekly atezolizumab increase the 6 months PFS rate, as evaluated from maintenance treatment initiation, compared to historical results with standard atezolizumab maintenance monotherapy in patients with ES SCLC non-progressive after four cycles of first-line chemo-immunotherapy induction with atezolizumab plus carboplatin and etoposide?

Timeline

Start

2023-01

Primary completion

2025-01

Completion

2029-01

Publications

• Background Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3. doi: 10.1038/s41572-020-00235-0.
• Background Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.
• Background Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13.
• Background Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remirez A, Lecanda F, Alignani D, Lasarte JJ, Macaya I, Senent Y, Bertolo C, Sainz C, Gil-Bazo I, Eguren-Santamaria I, Lopez-Picazo JM, Gonzalez A, Perez-Gracia JL, de Andrea CE, Vicent S, Sanmamed MF, Montuenga LM, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nat Cancer. 2020 Jan;1(1):75-85. doi: 10.1038/s43018-019-0007-9. Epub 2020 Jan 13.
• Background Vernieri C, Fuca G, Ligorio F, Huber V, Vingiani A, Iannelli F, Raimondi A, Rinchai D, Frige G, Belfiore A, Lalli L, Chiodoni C, Cancila V, Zanardi F, Ajazi A, Cortellino S, Vallacchi V, Squarcina P, Cova A, Pesce S, Frati P, Mall R, Corsetto PA, Rizzo AM, Ferraris C, Folli S, Garassino MC, Capri G, Bianchi G, Colombo MP, Minucci S, Foiani M, Longo VD, Apolone G, Torri V, Pruneri G, Bedognetti D, Rivoltini L, de Braud F. Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. Cancer Discov. 2022 Jan;12(1):90-107. doi: 10.1158/2159-8290.CD-21-0030. Epub 2021 Nov 17.
• Background Ligorio F, Fuca G, Provenzano L, Lobefaro R, Zanenga L, Vingiani A, Belfiore A, Lorenzoni A, Alessi A, Pruneri G, de Braud F, Vernieri C. Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. Eur J Cancer. 2022 Sep;172:300-310. doi: 10.1016/j.ejca.2022.05.046. Epub 2022 Jul 8.

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