@article{57c5a6f6367d4eaf9910fa9506567dd8,
title = "Phase I study of the CD47 blocker TTI-621 in patients with relapsed or refractory hematologic malignancies",
abstract = "Purpose: TTI-621 (SIRPα-IgG1 Fc) is a novel checkpoint inhibitor that activates antitumor activity by blocking the CD47 {"}don't eat me{"}signal. This first-in-human phase I study (NCT02663518) evaluated the safety and activity of TTI-621 in relapsed/refractory (R/R) hematologic malignancies. Patients and Methods: Patients with R/R lymphoma received escalating weekly intravenous TTI-621 to determine the maximum tolerated dose (MTD). During expansion, patients with various malignancies received weekly single-agent TTI-621 at the MTD; TTI-621 was combined with rituximab in patients with B-cell non- Hodgkin lymphoma (B-NHL) or with nivolumab in patients with Hodgkin lymphoma. The primary endpoint was the incidence/ severity of adverse events (AEs). Secondary endpoint included overall response rate (ORR). Results: Overall, 164 patients received TTI-621: 18 in escalation and 146 in expansion (rituximab combination, n = 35 and nivolumab combination, n = 4). On the basis of transient grade 4 thrombocytopenia, the MTD was determined as 0.2 mg/kg; 0.1 mg/kg was evaluated in combination cohorts. AEs included infusion-related reactions, thrombocytopenia, chills, and fatigue. Thrombocytopenia (20%, grade ≥3) was reversible between doses and not associated with bleeding. Transient thrombocytopenia that determined the initial MTD may not have been dose limiting. The ORR for all patients was 13%. The ORR was 29% (2/7) for diffuse large B-cell lymphoma (DLBCL) and 25% (8/32) for T-cell NHL (T-NHL) with TTI-621 monotherapy and was 21% (5/24) for DLBCL with TTI-621 plus rituximab. Further dose optimization is ongoing. Conclusions: TTI-621 was well-tolerated and demonstrated activity as monotherapy in patients with R/R B-NHL and T-NHL and combined with rituximab in patients with R/R B-NHL. ",
author = "Ansell, {Stephen M.} and Maris, {Michael B.} and Lesokhin, {Alexander M.} and Chen, {Robert W.} and Flinn, {Ian W.} and Ahmed Sawas and Minden, {Mark D.} and Diego Villa and Percival, {Mary Elizabeth M.} and Advani, {Anjali S.} and Foran, {James M.} and Horwitz, {Steven M.} and Mei, {Matthew G.} and Jasmine Zain and Savage, {Kerry J.} and Christiane Querfeld and Akilov, {Oleg E.} and Johnson, {Lisa D.S.} and Tina Catalano and Petrova, {Penka S.} and Uger, {Robert A.} and Sievers, {Eric L.} and Anca Milea and Kathleen Roberge and Yaping Shou and O'Connor, {Owen A.}",
note = "Funding Information: This study was funded by Trillium Therapeutics Inc. Medical writing support was provided by Ben Scott (Scott Medical Communications, LLC) and was funded by Trillium Therapeutics Inc. S.M. Ansell was funded in part by the National Institutes of Health (P50 CA097274). Funding Information: S.M. Ansell reported other from Trillium during the conduct of the study, and other from Bristol Myers Squibb, Seattle Genetics, Takeda, ADC Therapeutics, Regeneron, and Affimed outside the submitted work. A.M. Lesokhin reported grants from Trillium Therapeutics during the conduct of the study, as well as had a patent for prediction of responsiveness to treatment with immunomodulatory therapeutics licensed and with royalties paid from Serametrix, Inc. I.W. Flinn reported grants and other from AbbVie, AstraZeneca, BeiGene, Genentech, Gilead Sciences, Janssen, Juno Therapeutics, Kite Pharma, MorphoSys, Pharmacyclics, Roche, Seattle Genetics, Takeda, TG Therapeutics, Unum Therapeutics, and Verastem, other from Great Point Partners, Iksuda Therapeutics, Nurix Therapeutics, and Yingli Pharmaceuticals, and grants from Acerta Pharma, Agios, ArQule, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Curis, Forma Therapeutics, Forty Seven, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Karyopharm Therapeutics, Loxo, Merck, Novartis, Pfizer, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Teva, Trillium Therapeutics, and Triphase Research & Development Corp. outside the submitted work. D. Villa reported grants from Trillium Therapeutics during the conduct of the study and personal fees from Roche, Celgene, AbbVie, Seattle Genetics, Lundbeck, AstraZeneca, Kite/Gilead, Immunovaccine, NanoString, Sandoz Canada, and Purdue Pharma outside the submitted work. M.-E.M. Percival reported research funding from Trillium during the conduct of the study and other from AbbVie, Biosight, Cardiff Oncology, Genentech, Glycomimetics, Nohla Therapeutics, Oscotec, and Pfizer outside the submitted work. A.S. Advani reported other from Trillium during the conduct of the study, personal fees from Kite Pharmaceuticals, grants and personal fees from Amgen, Glycomimetics, Seattle Genetics, and Pfizer, and grants from AbbVie, Macrogenics, Immunogen, and Millenium outside the submitted work. J.M. Foran reported grants from Trillium during the conduct of the study, personal fees from Syros, Certara, Sanofi, Novartis, Pfizer, Servier, and Revolution Medicine, and grants from AbbVie, Boehringer Ingelheim, Actinium, Aprea, Aptose, H3Bioscience, Kura Oncology, Tolero, Xencor, and Takeda outside the submitted work. S.M. Horwitz reported grants and personal fees from Trillium during the conduct of the study, and grants and personal fees from Verastem, Trillium Therapeutics, Takeda, Seattle Genetics, Kyowa Hakko Kirin, Celgene, ADC Therapeutics, Affimed, Aileron, Forty Seven, Inc., Portola Pharmaceuticals, and Corvus, personal fees from Vividion Therapeutics, Myeloid Therapeutics, Kura Oncology, Janssen, C4 Therapeutics, Merck, Astex, Mundipharma, BMS, Innate Pharma, Miragen, and BeiGene, and grants from Daiichi Sankyo outside the submitted work. M.G. Mei reported personal fees from Morphosys and Sanofi-Genzyme outside the submitted work. J. Zain reported personal fees from Seattle Genetics, Verastem, Kiowa Kirin, and Mundi Pharma outside the submitted work. K.J. Savage reported other from BMS, Merck, Novartis, Gilead, AstraZeneca, AbbVie, Seattle Genetics, Kyowa, and Servier outside the submitted work. C. Querfeld reported personal fees, nonfinancial support, and other from Trillium during the conduct of the study, personal fees and other from Miragen, other from Bioniz, personal fees from Kyowa, grants from Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",
year = "2021",
month = apr,
doi = "10.1158/1078-0432.CCR-20-3706",
language = "English (US)",
volume = "27",
pages = "2190--2199",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",
}