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DRUG:

ontorpacept (PF-07901800)

i
Other names: PF-07901800, TTI-621, SIRPαFc, SIRPalphaFc, TTI 621, CD47 antigen/SIRPalpha protein modulator, TTI-621 intravenous, TTI621, PF 07901800, PF07901800
Associations
Company:
Pfizer
Drug class:
CD47 inhibitor
Associations
2ms
Enrollment change • Combination therapy
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
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ALK positive • BCL6 rearrangement • BCL2 rearrangement
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Keytruda (pembrolizumab) • maplirpacept (TTI-622) • ontorpacept (PF-07901800)
6ms
Phase classification
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Opdivo (nivolumab) • Rituxan (rituximab) • ontorpacept (PF-07901800)
9ms
TTI-621-03: A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma (clinicaltrials.gov)
P2, N=76, Terminated, Pfizer | Phase classification: P1/2 --> P2 | Active, not recruiting --> Terminated; Pfizer decided to terminate the study for administrative reasons. The termination was neither due to safety concerns nor a request from the regulatory authorities.
Phase classification • Trial termination • Combination therapy • Metastases
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doxorubicin hydrochloride • ontorpacept (PF-07901800)
over1year
Phase classification • Combination therapy • Metastases
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doxorubicin hydrochloride • ontorpacept (PF-07901800)
over1year
Enrollment open • Combination therapy
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
ALK positive • BCL6 rearrangement • BCL2 rearrangement
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Keytruda (pembrolizumab) • maplirpacept (TTI-622) • ontorpacept (PF-07901800)
over1year
Blockade of the Immune Checkpoint CD47 by TTI-621 Potentiates the Response to Anti-PD-L1 in Cutaneous T Cell Lymphoma. (PubMed, J Invest Dermatol)
We investigated the relationship between MYC and CD47 and PD-L1 expression and found that MYC shRNA knockdown and MYC functional suppression by TTI-621 (SIRPαFc) and anti-PD-L1 (durvalumab) in CTCL cell lines reduced the expression of CD47 and PD-L1 mRNA and protein as measured by qPCR and flow cytometry, respectively. These effects were mediated by cell‒death-related pathways, including apoptosis, autophagy, and necroptosis. Collectively, our findings demonstrate that CD47 and PD-L1 are critical regulators of immune surveillance in CTCL and dual targeting of CD47 and PD-L1 will provide insight into tumor immunotherapy for CTCL.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
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PD-L1 expression • MYC expression • CD47 expression
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Imfinzi (durvalumab) • ontorpacept (PF-07901800)
2years
Blockade of the Immune Checkpoint CD47 By TTI-621 Potentiates the Response to Anti-PD-L1 in Cutaneous T Cell Lymphoma (ASH 2022)
CTCL specimens at baseline and during treatment with anti-CD47/SIRPα (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.
PD(L)-1 Biomarker • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
|
PD-L1 expression • MYC expression • CD47 overexpression • CD47 expression
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Imfinzi (durvalumab) • ontorpacept (PF-07901800)
2years
New P2 trial • Combination therapy
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
ALK positive • BCL6 rearrangement • BCL2 rearrangement
|
Keytruda (pembrolizumab) • maplirpacept (TTI-622) • ontorpacept (PF-07901800)
over2years
CD47 Blockade potentiates immunotherapy of durvalumab against cutaneous T cell lymphoma (AACR 2022)
Notably, TTI-621 (SIRPαFc) treatment decreased M2 macrophage, immature dendritic cells, and inhibitory receptors expressed natural killer cells in CTCL patients at the end of the treatment, compared to baseline. 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.
PD(L)-1 Biomarker • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
|
PD-L1 expression • PD-L1 overexpression • MYC expression • CD47 overexpression
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Imfinzi (durvalumab) • ontorpacept (PF-07901800)
almost3years
Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sézary syndrome: a multicentre, phase 1 study. (PubMed, Lancet Haematol)
Intralesional TTI-621 was well tolerated and had activity in adjacent or distal non-injected lesions in patients with relapsed or refractory mycosis fungoides or Sézary syndrome, suggesting it has systemic and locoregional abscopal effects and potential as an immunotherapy for these conditions.
Clinical • P1 data • Clinical Trial,Phase I • Journal
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SIRPA (Signal Regulatory Protein Alpha)
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Keytruda (pembrolizumab) • ontorpacept (PF-07901800)
3years
Journal
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SIRPA (Signal Regulatory Protein Alpha)
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ontorpacept (PF-07901800)
3years
Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies (ASH 2021)
Testing of TTI-621 in alternative dosing schedules is in progress. With demonstrated good tolerability and robust single agent antitumor activity in heavily pre-treated patients, additional testing of TTI-621 beyond relapsed/refractory lymphoma has started.
Clinical • P1 data
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CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
|
CD47 overexpression
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ontorpacept (PF-07901800)
almost4years
Phase 1 Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies. (PubMed, Clin Cancer Res)
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.
Clinical • P1 data • Journal
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CD47 (CD47 Molecule)
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Opdivo (nivolumab) • Rituxan (rituximab) • ontorpacept (PF-07901800)