drugset / Trial / NCT04969315
TT-10 (PORT-6) and TT-4 (PORT-7) as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors
Non-randomizedSequentialOpen-labelTreatment
Summary
The goal of this clinical trial is to evaluate TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in participants with advanced selected solid tumors, who have failed or are not eligible for standard of care. The main questions it aims to answer are: 1. To evaluate the safety and tolerability of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) 2. To determine the maximum tolerated dose or the recommended phase 2 dose of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) 3. To obtain a preliminary estimate of efficacy of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in advanced solid tumors.
Timeline
- Start
- 2023-06-23
- Primary completion
- 2026-06-01
- Completion
- 2027-12-31
Publications
- Background Zhang J, Yan W, Duan W, Wuthrich K, Cheng J. Tumor Immunotherapy Using A2A Adenosine Receptor Antagonists. Pharmaceuticals (Basel). 2020 Sep 8;13(9):237. doi: 10.3390/ph13090237.
- Background Allard B, Allard D, Buisseret L, Stagg J. The adenosine pathway in immuno-oncology. Nat Rev Clin Oncol. 2020 Oct;17(10):611-629. doi: 10.1038/s41571-020-0382-2. Epub 2020 Jun 8.
- Background Beavis PA, Henderson MA, Giuffrida L, Mills JK, Sek K, Cross RS, Davenport AJ, John LB, Mardiana S, Slaney CY, Johnstone RW, Trapani JA, Stagg J, Loi S, Kats L, Gyorki D, Kershaw MH, Darcy PK. Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy. J Clin Invest. 2017 Mar 1;127(3):929-941. doi: 10.1172/JCI89455. Epub 2017 Feb 6.
- Background Willingham SB, Hotson AN, Miller RA. Targeting the A2AR in cancer; early lessons from the clinic. Curr Opin Pharmacol. 2020 Aug;53:126-133. doi: 10.1016/j.coph.2020.08.003. Epub 2020 Sep 29.
- Background Vijayan D, Young A, Teng MWL, Smyth MJ. Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer. 2017 Dec;17(12):709-724. doi: 10.1038/nrc.2017.86. Epub 2017 Oct 23.
- Background Steingold JM, Hatfield SM. Targeting Hypoxia-A2A Adenosinergic Immunosuppression of Antitumor T Cells During Cancer Immunotherapy. Front Immunol. 2020 Sep 29;11:570041. doi: 10.3389/fimmu.2020.570041. eCollection 2020.
- Background Sek K, Molck C, Stewart GD, Kats L, Darcy PK, Beavis PA. Targeting Adenosine Receptor Signaling in Cancer Immunotherapy. Int J Mol Sci. 2018 Dec 2;19(12):3837. doi: 10.3390/ijms19123837.
- Background Vigano S, Alatzoglou D, Irving M, Menetrier-Caux C, Caux C, Romero P, Coukos G. Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function. Front Immunol. 2019 Jun 6;10:925. doi: 10.3389/fimmu.2019.00925. eCollection 2019.
- Background Schwarzacher SW, Krammer EB. Complex anomalies of the human aortic arch system: unique case with both vertebral arteries as additional branches of the aortic arch. Anat Rec. 1989 Nov;225(3):246-50. doi: 10.1002/ar.1092250310.
- Background Helms RS, Powell JD. Rethinking the adenosine-A2AR checkpoint: implications for enhancing anti-tumor immunotherapy. Curr Opin Pharmacol. 2020 Aug;53:77-83. doi: 10.1016/j.coph.2020.07.003. Epub 2020 Aug 9.
- Background Kamai T, Kijima T, Tsuzuki T, Nukui A, Abe H, Arai K, Yoshida KI. Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival. Cancer Immunol Immunother. 2021 Jul;70(7):2009-2021. doi: 10.1007/s00262-020-02843-x. Epub 2021 Jan 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.