- |||||||||| ontorpacept (TTI-621) / Pfizer
Blockade of the Immune Checkpoint CD47 By TTI-621 Potentiates the Response to Anti-PD-L1 in Cutaneous T Cell Lymphoma (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_3246; P1, P1/2 CTCL specimens at baseline and during treatment with anti-CD47/SIRPa (TTI621) and anti-PD-L1 (durvalumab) were used to analyze immune cell gene expression. Collectively, our findings demonstrate that CD47 and PD-L1 are critical regulators of the immune microenvironment in CTCL and that dual targeting of CD47 and PD-L1 may potentiate anti-tumor responses in CTCL.
- |||||||||| ontorpacept (TTI-621) / Pfizer
Journal: Emerging drugs for the treatment of cutaneous T-cell lymphoma. (Pubmed Central) - Apr 6, 2022 Durvalumab, pembrolizumab, TTI-621, BNZ-1, and MRG-106 are several of the emerging treatments still in trials. Further combinatorial studies are needed as none of the treatments have demonstrated long term remissions.
- |||||||||| Imfinzi (durvalumab) / AstraZeneca
CD47 Blockade potentiates immunotherapy of durvalumab against cutaneous T cell lymphoma (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6481; RNA-sequencing analysis indicated that these effects were mediated by cell death related pathways such as apoptosis, autophagy, and necroptosis. Collectively, our findings demonstrated that CD47 and PD-L1 are critical regulators of innate and adaptive immune surveillance in CTCL and that dual targeting of CD47 and PD-L1 will provide insight into tumor immunotherapy to improve tumor control in CTCL.
- |||||||||| ontorpacept (PF-07901800) / Pfizer
Trial completion date, Trial primary completion date: A Trial of PF-07901800 (TTI-621) for Patients With Hematologic Malignancies and Selected Solid Tumors (clinicaltrials.gov) - Feb 1, 2022 P1a/1b, N=260, Recruiting, Collectively, our findings demonstrated that CD47 and PD-L1 are critical regulators of innate and adaptive immune surveillance in CTCL and that dual targeting of CD47 and PD-L1 will provide insight into tumor immunotherapy to improve tumor control in CTCL. Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Just eat it: A review of CD47 and SIRP-α antagonism. (Pubmed Central) - Jan 23, 2021
This review summarizes the status of key CD47 antagonists in clinical trials, including the biologics, Hu5F9-G4 (5F9), TTI-621, and ALX148, as well as the small molecule, RRx-001, now in a Phase 3 clinical trial, which has not been previously included in CD47-SIRPα reviews focused on biologics. Hu5F9-G4 (5F9), TTI-621, ALX148, and RRx-001 are chosen as compounds with potentially promising data that have advanced the farthest in clinical development.
- |||||||||| ontorpacept (PF-07901800) / Pfizer
Trial completion date, Trial primary completion date: A Trial of PF-07901800 (TTI-621) for Patients With Hematologic Malignancies and Selected Solid Tumors (clinicaltrials.gov) - Nov 27, 2020 P1a/1b, N=260, Recruiting, Hu5F9-G4 (5F9), TTI-621, ALX148, and RRx-001 are chosen as compounds with potentially promising data that have advanced the farthest in clinical development. Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021
- |||||||||| ontorpacept (TTI-621) / Trillium Therap
Journal: Targeting CD47 in Sézary syndrome with SIRPαFc. (Pubmed Central) - Jul 25, 2020 P1a/1b We conclude that inhibition of the CD47-SIRPα signaling pathway has therapeutic benefit for patients with SS. This trial was registered at www.clinicaltrials.gov as #NCT02663518.
- |||||||||| TTI-621 / Trillium Therapeutics
Sirpαfc Treatment Targets Human Acute Myeloid Leukemia Stem Cells (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5636; TTI-621 (Trillium Therapeutics Inc., Ontario, Canada) is a human SIRPαFc protein formed by fusing the IgV doman of human SIRPα to a human IgG1-Fc moiety; it is designed to bind CD47 on leukemia cells and disrupt its interaction with SIRPα on host macrophages...Our data demonstrate that SIRPαFc effectively targets LSCs in a human AML xenotransplantion model with high response rates across a heterogeneous cohort of primary AML samples, including samples with unfavorable risk features . SIRPαFc may be most effective in the remission setting as maintenance therapy for patients with detectable residual disease, to eradicate residual LSCs and prevent relapse.
- |||||||||| ontorpacept (TTI-621) / Trillium Therap
Journal, IO biomarker: Targeting CD47 as a cancer therapeutic strategy: the cutaneous T-cell lymphoma experience. (Pubmed Central) - Apr 11, 2019 In the CTCL tumor microenvironment, increased immune checkpoint inhibition expression via CD47 bound to SIRPα correlates with a more advanced disease state. Continued success in treating these patients requires further studies on CD47 antagonists, specifically when combined with other antibodies.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review. (Pubmed Central) - Mar 23, 2019 Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.
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