The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2

Summary

This is a randomized trial evaluating the efficacy and safety of sequential dual-agent immunotherapy and risk-adapted radiotherapy for patients with locally advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score of at least 50%. Participants will be randomized between two dual-agent immunotherapy regimens: durvalumab + monalizumab versus durvalumab + oleclumab.

Timeline

Start

2026-09

Primary completion

2028-04

Completion

2029-02

Publications

• Background Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
• Background Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
• Background Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29.
• Background Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. doi: 10.1200/JCO.19.01162. Epub 2019 Dec 16.
• Background Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.
• Background Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.
• Background Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, Albain K, Sause WT, Curran WJ. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):425-34. doi: 10.1016/j.ijrobp.2010.09.004. Epub 2010 Oct 25.
• Background Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):516-7. doi: 10.1016/s0360-3016(99)00364-8. No abstract available.
• Background Shaverdian N, Offin MD, Rimner A, Shepherd AF, Wu AJ, Rudin CM, Hellmann MD, Chaft JE, Gomez DR. Utilization and factors precluding the initiation of consolidative durvalumab in unresectable stage III non-small cell lung cancer. Radiother Oncol. 2020 Mar;144:101-104. doi: 10.1016/j.radonc.2019.11.015. Epub 2019 Nov 28.
• Background Bruni A, Scotti V, Borghetti P, Vagge S, Cozzi S, D'Angelo E, Giaj Levra N, Fozza A, Taraborrelli M, Piperno G, Vanoni V, Sepulcri M, Trovo M, Nardone V, Lattanzi E, Bou Selman S, Bertolini F, Franceschini D, Agustoni F, Jereczek-Fossa BA, Magrini SM, Livi L, Lohr F, Filippi AR. A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer. Front Oncol. 2021 Sep 28;11:744956. doi: 10.3389/fonc.2021.744956. eCollection 2021.
• Background Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. doi: 10.1200/JCO.18.00149. Epub 2019 Jan 8.
• Background Ohri N, Bodner WR, Halmos B, Cheng H, Perez-Soler R, Keller SM, Kalnicki S, Garg M. 18F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):372-380. doi: 10.1016/j.ijrobp.2016.10.031. Epub 2016 Oct 26.
• Background Ohri N, Piperdi B, Garg MK, Bodner WR, Gucalp R, Perez-Soler R, Keller SM, Guha C. Pre-treatment FDG-PET predicts the site of in-field progression following concurrent chemoradiotherapy for stage III non-small cell lung cancer. Lung Cancer. 2015 Jan;87(1):23-7. doi: 10.1016/j.lungcan.2014.10.016. Epub 2014 Nov 6.
• Background Binkley MS, Koenig JL, Kashyap M, Xiang M, Liu Y, Sodji Q, Maxim PG, Diehn M, Loo BW Jr, Gensheimer MF. Predicting per-lesion local recurrence in locally advanced non-small cell lung cancer following definitive radiation therapy using pre- and mid-treatment metabolic tumor volume. Radiat Oncol. 2020 May 19;15(1):114. doi: 10.1186/s13014-020-01546-y.
• Background Ohri N, Bodner WR, Kabarriti R, Shankar V, Cheng H, Abraham T, Halmos B, Gucalp R, Perez-Soler R, Kalnicki S, Garg M. Positron Emission Tomography-Adjusted Intensity Modulated Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):709-715. doi: 10.1016/j.ijrobp.2017.10.032. Epub 2017 Oct 28.
• Background Dess RT, Sun Y, Matuszak MM, Sun G, Soni PD, Bazzi L, Murthy VL, Hearn JWD, Kong FM, Kalemkerian GP, Hayman JA, Ten Haken RK, Lawrence TS, Schipper MJ, Jolly S. Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2017 May 1;35(13):1395-1402. doi: 10.1200/JCO.2016.71.6142. Epub 2017 Mar 16.
• Background Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, Mavroidis P, Lee CB, Jensen BC, Rosenman JG, Socinski MA, Stinchcombe TE, Marks LB. Cardiac Toxicity After Radiotherapy for Stage III Non-Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy. J Clin Oncol. 2017 May 1;35(13):1387-1394. doi: 10.1200/JCO.2016.70.0229. Epub 2017 Jan 23.
• Background Contreras JA, Lin AJ, Weiner A, Speirs C, Samson P, Mullen D, Campian J, Bradley J, Roach M, Robinson C. Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer. Radiother Oncol. 2018 Sep;128(3):498-504. doi: 10.1016/j.radonc.2018.05.017. Epub 2018 May 30.
• Background Chen D, Patel RR, Verma V, Ramapriyan R, Barsoumian HB, Cortez MA, Welsh JW. Interaction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapy. Radiother Oncol. 2020 Sep;150:114-120. doi: 10.1016/j.radonc.2020.05.051. Epub 2020 Jun 7.
• Background Tang C, Liao Z, Gomez D, Levy L, Zhuang Y, Gebremichael RA, Hong DS, Komaki R, Welsh JW. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1084-1091. doi: 10.1016/j.ijrobp.2014.04.025. Epub 2014 Jul 8.
• Background Darragh LB, Gadwa J, Pham TT, Van Court B, Neupert B, Olimpo NA, Nguyen K, Nguyen D, Knitz MW, Hoen M, Corbo S, Joshi M, Zhuang Y, Amann M, Wang XJ, Dow S, Kedl RM, Samedi V, Boss MK, Karam SD. Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors. Nat Commun. 2022 Nov 16;13(1):7015. doi: 10.1038/s41467-022-34676-w.
• Background Ohri N, Jolly S, Cooper BT, Kabarriti R, Bodner WR, Klein J, Guha C, Viswanathan S, Shum E, Sabari JK, Cheng H, Gucalp RA, Castellucci E, Qin A, Gadgeel SM, Halmos B. Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT). J Clin Oncol. 2024 Feb 10;42(5):562-570. doi: 10.1200/JCO.23.00627. Epub 2023 Nov 21.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med. 2009 May;50 Suppl 1(Suppl 1):122S-50S. doi: 10.2967/jnumed.108.057307.
• Background Basch E, Becker C, Rogak LJ, Schrag D, Reeve BB, Spears P, Smith ML, Gounder MM, Mahoney MR, Schwartz GK, Bennett AV, Mendoza TR, Cleeland CS, Sloan JA, Bruner DW, Schwab G, Atkinson TM, Thanarajasingam G, Bertagnolli MM, Dueck AC. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Clin Trials. 2021 Feb;18(1):104-114. doi: 10.1177/1740774520975120. Epub 2020 Dec 1.
• Background Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, Bruner DW, Cleeland CS, Sloan JA, Chilukuri R, Baumgartner P, Denicoff A, St Germain D, O'Mara AM, Chen A, Kelaghan J, Bennett AV, Sit L, Rogak L, Barz A, Paul DB, Schrag D. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014 Sep 29;106(9):dju244. doi: 10.1093/jnci/dju244. Print 2014 Sep.
• Background Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, Watkins A, Mullins S, Chodorge M, Andrews J, Bannister D, Dick E, Crawford N, Parmentier J, Alimzhanov M, Babcook JS, Foltz IN, Buchanan A, Bedian V, Wilkinson RW, McCourt M. Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody. Cancer Immunol Res. 2015 Sep;3(9):1052-62. doi: 10.1158/2326-6066.CIR-14-0191. Epub 2015 May 5.
• Background Narwal R, Roskos LK, Robbie GJ. Population pharmacokinetics of sifalimumab, an investigational anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus. Clin Pharmacokinet. 2013 Nov;52(11):1017-27. doi: 10.1007/s40262-013-0085-2.
• Background Ng CM, Lum BL, Gimenez V, Kelsey S, Allison D. Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis. Pharm Res. 2006 Jun;23(6):1275-84. doi: 10.1007/s11095-006-0205-x. Epub 2006 May 26.
• Background Wang DD, Zhang S, Zhao H, Men AY, Parivar K. Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J Clin Pharmacol. 2009 Sep;49(9):1012-24. doi: 10.1177/0091270009337512. Epub 2009 Jul 20.
• Background Zhang S, Shi R, Li C, Parivar K, Wang DD. Fixed dosing versus body size-based dosing of therapeutic peptides and proteins in adults. J Clin Pharmacol. 2012 Jan;52(1):18-28. doi: 10.1177/0091270010388648. Epub 2011 Jan 13.
• Background Shiraishi Y, Fang P, Xu C, Song J, Krishnan S, Koay EJ, Mehran RJ, Hofstetter WL, Blum-Murphy M, Ajani JA, Komaki R, Minsky B, Mohan R, Hsu CC, Hobbs BP, Lin SH. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy. Radiother Oncol. 2018 Jul;128(1):154-160. doi: 10.1016/j.radonc.2017.11.028. Epub 2017 Dec 14.
• Background Abravan A, Faivre-Finn C, Kennedy J, McWilliam A, van Herk M. Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer. J Thorac Oncol. 2020 Oct;15(10):1624-1635. doi: 10.1016/j.jtho.2020.06.008. Epub 2020 Jun 14.
• Background Friedes C, Chakrabarti T, Olson S, Prichett L, Brahmer JR, Forde PM, Voong RK, Marrone KA, Lam VK, Hann CL, Broderick SR, Battafarano RJ, Ha JS, Bush EL, Yang SC, Hales RK, Feliciano JL. Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy. Lung Cancer. 2021 Apr;154:36-43. doi: 10.1016/j.lungcan.2021.01.022. Epub 2021 Jan 27.
• Background Le Drean E, Vely F, Olcese L, Cambiaggi A, Guia S, Krystal G, Gervois N, Moretta A, Jotereau F, Vivier E. Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases. Eur J Immunol. 1998 Jan;28(1):264-76. doi: 10.1002/(SICI)1521-4141(199801)28:013.0.CO;2-O.
• Background McMahon CW, Raulet DH. Expression and function of NK cell receptors in CD8+ T cells. Curr Opin Immunol. 2001 Aug;13(4):465-70. doi: 10.1016/s0952-7915(00)00242-9.
• Background Navarro F, Llano M, Bellon T, Colonna M, Geraghty DE, Lopez-Botet M. The ILT2(LIR1) and CD94/NKG2A NK cell receptors respectively recognize HLA-G1 and HLA-E molecules co-expressed on target cells. Eur J Immunol. 1999 Jan;29(1):277-83. doi: 10.1002/(SICI)1521-4141(199901)29:013.0.CO;2-4.
• Background Talebian Yazdi M, van Riet S, van Schadewijk A, Fiocco M, van Hall T, Taube C, Hiemstra PS, van der Burg SH. The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma. Oncotarget. 2016 Jan 19;7(3):3477-88. doi: 10.18632/oncotarget.6506.
• Background Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, Andre P, Dieu-Nosjean MC, Alifano M, Regnard JF, Fridman WH, Sautes-Fridman C, Cremer I. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 2011 Aug 15;71(16):5412-22. doi: 10.1158/0008-5472.CAN-10-4179. Epub 2011 Jun 27.
• Background Herbst RS, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez-Hernandez A, Dakhil S, Camidge DR, Winzer L, Soo-Hoo Y, Cooper ZA, Kumar R, Bothos J, Aggarwal C, Martinez-Marti A. COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Oct 10;40(29):3383-3393. doi: 10.1200/JCO.22.00227. Epub 2022 Apr 22.
• Background Antonioli L, Blandizzi C, Pacher P, Hasko G. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer. 2013 Dec;13(12):842-57. doi: 10.1038/nrc3613. Epub 2013 Nov 14.
• Background Gotay CC, Kawamoto CT, Bottomley A, Efficace F. The prognostic significance of patient-reported outcomes in cancer clinical trials. J Clin Oncol. 2008 Mar 10;26(8):1355-63. doi: 10.1200/JCO.2007.13.3439. Epub 2008 Jan 28.
• Background Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16.
• Background Fogh SE, Deshmukh S, Berk LB, Dueck AC, Roof K, Yacoub S, Gergel T, Stephans K, Rimner A, DeNittis A, Pablo J, Rineer J, Williams TM, Bruner D. A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy-Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012. Int J Radiat Oncol Biol Phys. 2017 Mar 15;97(4):786-796. doi: 10.1016/j.ijrobp.2016.11.022. Epub 2016 Nov 23.
• Background Ohri N, Kabarriti R, Bodner WR, Mehta KJ, Shankar V, Halmos B, Haigentz M Jr, Rapkin B, Guha C, Kalnicki S, Garg M. Continuous Activity Monitoring During Concurrent Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):1061-1065. doi: 10.1016/j.ijrobp.2016.12.030. Epub 2016 Dec 25.
• Background Ohri N, Halmos B, Bodner WR, Cheng H, Guha C, Kalnicki S, Garg M. Daily Step Counts: A New Prognostic Factor in Locally Advanced Non-Small Cell Lung Cancer? Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):745-751. doi: 10.1016/j.ijrobp.2019.07.055. Epub 2019 Aug 7.
• Background Ewald B, Duke J, Thakkinstian A, Attia J, Smith W. Physical activity of older Australians measured by pedometry. Australas J Ageing. 2009 Sep;28(3):127-33. doi: 10.1111/j.1741-6612.2009.00372.x.
• Background Paul S, Bodner WR, Garg M, Tang J, Ohri N. Cardiac Irradiation Predicts Activity Decline in Patients Receiving Concurrent Chemoradiation for Locally Advanced Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):597-601. doi: 10.1016/j.ijrobp.2020.05.042. Epub 2020 Jun 1.
• Background Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis. 1974 Sep;27(7-8):365-75. doi: 10.1016/0021-9681(74)90015-0. No abstract available.
• Background Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, Almeida FD, Xiao Y, Ohri N, Brockway KD, Piper JW, Nelson AS. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):1164-71. doi: 10.1016/j.ijrobp.2010.12.055. Epub 2011 Apr 29.

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Indications