A Study of Anti-PD-1 Combinations of D-CIK Immunotherapy and Axitinib in Advanced Ranal Carcinoma

Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and low dose anti-PD-1 antibody in patients with metastatic renal cell carcinoma treated with axitinib.

Sex

All

Inclusion Criteria:

* advanced renal clear cell carcinoma confirmed by pathology: high-volume disease without systemic treatment(including primary lesion unable to surgery, multiple lymph node metastases or distant metastases), or achieved disease progression after treatment by the anti-angiogenesis therapy (TKI or mTOR inhibitors) or by cytokines or combination therapy
* Predicted survival \>=3 months
* At least 1 measurable lesion

High-volume disease（meet one of the following criteria）:1. More than 3 sites of lesions with or without primary lesions, and at least 1 lesion routine CT or spiral CT scan \>=3cm; 2. Unresected primary lesions (\> 10cm), accompanied by 2 metastatic lesions; 3. After nephrectomy, single metastasis, at least 3 metastases, and at least one lesion \> 2cm; 4. After nephrectomy, multiple metastatic(\>3 organs) and at least one lesion \> 2cm.

Exclusion Criteria:

* Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib
* Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components
* Severe cardiovascular and cerebrovascular diseases, uncontrollable severe hypertension and diabetes, severe renal insufficiency or uremia
* Long-term use of immunosuppressive agents after organ transplantation
* Immunosuppressive drugs are currently in use
* People with a clear and serious infection
* Predicted survival\<3 months
* Patients with T cell lymphoma, myeloma
* Patients with autoimmune diseases
* HIV positive, or other immunodeficiency diseases
* Pregnant or nursing

• RESULTRini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4. PMID 22056247
• RESULTDu Four S, Maenhout SK, De Pierre K, Renmans D, Niclou SP, Thielemans K, Neyns B, Aerts JL. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. Oncoimmunology. 2015 Jan 22;4(4):e998107. doi: 10.1080/2162402X.2014.998107. eCollection 2015 Apr. PMID 26137411
• RESULTMahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015 Aug;14(8):561-84. doi: 10.1038/nrd4591. PMID 26228759
• RESULTLee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4. PMID 25747273
• RESULTChen CL, Pan QZ, Weng DS, Xie CM, Zhao JJ, Chen MS, Peng RQ, Li DD, Wang Y, Tang Y, Wang QJ, Zhang ZL, Zhang XF, Jiang LJ, Zhou ZQ, Zhu Q, He J, Liu Y, Zhou FJ, Xia JC. Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with advanced solid tumors. Oncoimmunology. 2018 Jan 10;7(4):e1417721. doi: 10.1080/2162402X.2017.1417721. eCollection 2018. PMID 29632736