Phase II Study of Toripalimab Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis

Summary

Metastatic colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The introduction of immune-checkpoint inhibition (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer. Stereotactic body radiation therapy (SBRT) delivers a large dose of radiation to the tumor target with high precision while sparing irradiation of the surrounding normal tissues. It is suggested that SBRT could be the most appropriate radiotherapy modality to be combined with immunotherapy since it induces the expression of a series of cytokines and new tumour-associated antigens (TAAs) and is more likely to cause intense immune response and exert an abscopal effect than conventional radiotherapy. Thus, this study is to explore the use of SBRT in combination with ICI in colorectal cancer patients with oligometastasis, in order to get better local and systemic tumor control and improve progress-free survival (PFS).

Timeline

Start

2019-03-01

Primary completion

2021-03-01

Completion

2021-09-01

Publications

• Background Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.
• Background Petrelli F, Comito T, Barni S, Pancera G, Scorsetti M, Ghidini A; SBRT for CRC liver metastases. Stereotactic body radiotherapy for colorectal cancer liver metastases: A systematic review. Radiother Oncol. 2018 Dec;129(3):427-434. doi: 10.1016/j.radonc.2018.06.035. Epub 2018 Jul 9.
• Background Joo JH, Park JH, Kim JC, Yu CS, Lim SB, Park IJ, Kim TW, Hong YS, Kim KP, Yoon SM, Park J, Kim JH. Local Control Outcomes Using Stereotactic Body Radiation Therapy for Liver Metastases From Colorectal Cancer. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):876-883. doi: 10.1016/j.ijrobp.2017.07.030. Epub 2017 Jul 31.
• Background Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, Al-Hallaq HA, Arina A, Khodarev NN, Janisch L, Chang P, Patel JD, Fleming GF, Moroney J, Sharma MR, White JR, Ratain MJ, Gajewski TF, Weichselbaum RR, Chmura SJ. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018 Jun 1;36(16):1611-1618. doi: 10.1200/JCO.2017.76.2229. Epub 2018 Feb 13.
• Background Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6.
• Background Tang C, Welsh JW, de Groot P, Massarelli E, Chang JY, Hess KR, Basu S, Curran MA, Cabanillas ME, Subbiah V, Fu S, Tsimberidou AM, Karp D, Gomez DR, Diab A, Komaki R, Heymach JV, Sharma P, Naing A, Hong DS. Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells. Clin Cancer Res. 2017 Mar 15;23(6):1388-1396. doi: 10.1158/1078-0432.CCR-16-1432. Epub 2016 Sep 20.
• Background Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengelov L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR; CA184-043 Investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):700-12. doi: 10.1016/S1470-2045(14)70189-5. Epub 2014 May 13.
• Background Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017 May 4;545(7652):60-65. doi: 10.1038/nature22079. Epub 2017 Apr 10.
• Background Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, Xia H, Man Q, Zhong W, Antelo LF, Wu B, Xiong X, Liu X, Guan L, Li T, Liu S, Yang R, Lu Y, Dong L, McGettigan S, Somasundaram R, Radhakrishnan R, Mills G, Lu Y, Kim J, Chen YH, Dong H, Zhao Y, Karakousis GC, Mitchell TC, Schuchter LM, Herlyn M, Wherry EJ, Xu X, Guo W. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018 Aug;560(7718):382-386. doi: 10.1038/s41586-018-0392-8. Epub 2018 Aug 8.
• Background Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.
• Background Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, van As N, Tree A, Hatfield P, Harrow S, McDonald F, Ahmed M, Saran FH, Webster GJ, Khoo V, Landau D, Eaton DJ, Hawkins MA. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018 Jan;30(1):5-14. doi: 10.1016/j.clon.2017.09.007. Epub 2017 Oct 13.

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