PMID- 33451977
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20230721
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 27
IP  - 8
DP  - 2021 Apr 15
TI  - Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory 
      Hematologic Malignancies.
PG  - 2190-2199
LID - 10.1158/1078-0432.CCR-20-3706 [doi]
AB  - PURPOSE: TTI-621 (SIRPalpha-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.
CI  - (c)2021 American Association for Cancer Research.
FAU - Ansell, Stephen M
AU  - Ansell SM
AUID- ORCID: 0000-0003-1244-6758
AD  - Division of Hematology, Mayo Clinic, Rochester, Minnesota. 
      ansell.stephen@mayo.edu.
FAU - Maris, Michael B
AU  - Maris MB
AD  - Colorado Blood Cancer Institute and Sarah Cannon Research Institute, Denver, 
      Colorado.
FAU - Lesokhin, Alexander M
AU  - Lesokhin AM
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Chen, Robert W
AU  - Chen RW
AD  - Department of Hematology and Hematopoietic Transplantation, City of Hope Medical 
      Center, Duarte, California.
FAU - Flinn, Ian W
AU  - Flinn IW
AUID- ORCID: 0000-0001-6724-290X
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Tennessee Oncology, Nashville, Tennessee.
FAU - Sawas, Ahmed
AU  - Sawas A
AD  - Center for Lymphoid Malignancies, Columbia University Medical Center, College of 
      Physicians and Surgeons, New York, New York.
FAU - Minden, Mark D
AU  - Minden MD
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, 
      Canada.
FAU - Villa, Diego
AU  - Villa D
AUID- ORCID: 0000-0002-4625-3009
AD  - Division of Medical Oncology and Centre for Lymphoid Cancer, BC Cancer, 
      Vancouver, British Columbia, Canada.
FAU - Percival, Mary-Elizabeth M
AU  - Percival MM
AD  - Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington.
AD  - Division of Hematology, University of Washington, Seattle, Washington.
FAU - Advani, Anjali S
AU  - Advani AS
AD  - Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
FAU - Foran, James M
AU  - Foran JM
AD  - Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida.
FAU - Horwitz, Steven M
AU  - Horwitz SM
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Mei, Matthew G
AU  - Mei MG
AUID- ORCID: 0000-0002-1109-6955
AD  - Department of Hematology and Hematopoietic Transplantation, City of Hope Medical 
      Center, Duarte, California.
FAU - Zain, Jasmine
AU  - Zain J
AD  - Department of Hematology and Hematopoietic Transplantation, City of Hope Medical 
      Center, Duarte, California.
FAU - Savage, Kerry J
AU  - Savage KJ
AD  - Division of Medical Oncology and Centre for Lymphoid Cancer, BC Cancer, 
      Vancouver, British Columbia, Canada.
FAU - Querfeld, Christiane
AU  - Querfeld C
AD  - Department of Hematology and Hematopoietic Transplantation, City of Hope Medical 
      Center, Duarte, California.
FAU - Akilov, Oleg E
AU  - Akilov OE
AUID- ORCID: 0000-0003-1339-5710
AD  - Cutaneous Lymphoma Program, Department of Dermatology, University of Pittsburgh 
      Medical Center, Pittsburgh, Pennsylvania.
FAU - Johnson, Lisa D S
AU  - Johnson LDS
AUID- ORCID: 0000-0002-2019-6560
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Catalano, Tina
AU  - Catalano T
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Petrova, Penka S
AU  - Petrova PS
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Uger, Robert A
AU  - Uger RA
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Sievers, Eric L
AU  - Sievers EL
AUID- ORCID: 0000-0002-0794-9441
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Milea, Anca
AU  - Milea A
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Roberge, Kathleen
AU  - Roberge K
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - Shou, Yaping
AU  - Shou Y
AD  - Trillium Therapeutics Inc., Mississauga, Ontario, Canada.
FAU - O'Connor, Owen A
AU  - O'Connor OA
AD  - University of Virginia Cancer Center, Charlottesville, Virginia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02663518
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210115
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CD47 Antigen)
RN  - 0 (CD47 protein, human)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Immunoglobulin G)
RN  - 0 (TTI-621)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD47 Antigen/*antagonists & inhibitors
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Hematologic Neoplasms/*drug therapy/immunology
MH  - Humans
MH  - Immune Checkpoint Inhibitors/administration & dosage/*adverse effects
MH  - Immunoglobulin G/administration & dosage/*adverse effects
MH  - Infusions, Intravenous
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/immunology
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2021/01/17 06:00
MHDA- 2022/03/15 06:00
CRDT- 2021/01/16 05:31
PHST- 2020/09/18 00:00 [received]
PHST- 2020/11/23 00:00 [revised]
PHST- 2021/01/08 00:00 [accepted]
PHST- 2021/01/17 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/01/16 05:31 [entrez]
AID - 1078-0432.CCR-20-3706 [pii]
AID - 10.1158/1078-0432.CCR-20-3706 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2021 Apr 15;27(8):2190-2199. doi: 10.1158/1078-0432.CCR-20-3706. 
      Epub 2021 Jan 15.