A Phase 1/2, Open-Label Clinical Study To Evaluate Safety And Efficacy Of TP-0184 To Treat Anemia When Administered To Adult Patients With IPSS-R Low Or Intermediate Risk Myelodysplastic Syndromes

This study will evaluate preliminary safety and efficacy of TP-0184 to treat anemia when administered to adult patients with Revised International Prognostic Scoring System (IPSS-R) low or intermediate risk MDS. The recommended Phase 2 dose (RP2D) will be determined by the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the Phase 1 portion of the study.

Start Date28 Dec 2020

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

NCT03429218 / CompletedPhase 1

A Phase I, First-in-human, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0184 Administered Once Weekly for 4 Weeks to Patients With Advanced Solid Tumors

TP-0184 is a potent inhibitor of ALK2 or ACRV1 kinase, a constitutively active serine/threonine receptor kinase due to activating mutations or upregulated upstream signaling pathways. This is a Phase 1, open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks in patients with advanced solid tumors.

Start Date10 Jul 2018

Sponsor / Collaborator

Sumitomo Pharma America, Inc.

100 Clinical Results associated with Itacnosertib

100 Translational Medicine associated with Itacnosertib

100 Patents (Medical) associated with Itacnosertib

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01 Jan 2024·Leukemia

TP-0184 inhibits FLT3/ACVR1 to overcome FLT3 inhibitor resistance and hinder AML growth synergistically with venetoclax

Article

Author: Mollard, Alexis ; Yin, Zheng ; Hegde, Venkatesh L ; Kumar, Bijender ; Jaggupilli, Appalaraju ; Vankayalapati, Hariprasad ; El-Dana, Fouad ; Daver, Naval ; Battula, V Lokesh ; Borthakur, Gautam ; Puppala, Mamta ; Wong, Stephen T C ; Anand, Vivek ; Warner, Steven L ; Foulks, Jason M ; Yuan, Bin ; Tyagi, Anudishi ; Ly, Stanley

We identified activin A receptor type I (ACVR1), a member of the TGF-β superfamily, as a factor favoring acute myeloid leukemia (AML) growth and a new potential therapeutic target. ACVR1 is overexpressed in FLT3-mutated AML and inhibition of ACVR1 expression sensitized AML cells to FLT3 inhibitors. We developed a novel ACVR1 inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines. Molecular docking and in vitro kinase assays revealed that TP-0184 binds to both ACVR1 and FLT3 with high affinity and inhibits FLT3/ACVR1 downstream signaling. Treatment with TP-0184 or in combination with BCL2 inhibitor, venetoclax dramatically inhibited leukemia growth in FLT3-mutated AML cell lines and patient-derived xenograft models in a dose-dependent manner. These findings suggest that ACVR1 is a novel biomarker and plays a role in AML resistance to FLT3 inhibitors and that FLT3/ACVR1 dual inhibitor TP-0184 is a novel potential therapeutic tool for AML with FLT3 mutations.

100 Deals associated with Itacnosertib

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Anemia	Phase 2	US	Sumitomo Dainippon Pharma Oncology, Inc.Startup	28 Dec 2020
Myelodysplastic Syndromes	Phase 2	US	Sumitomo Pharma America, Inc.	28 Dec 2020
Solid tumor	Phase 2	US	Sumitomo Dainippon Pharma Oncology, Inc.Startup	10 Jul 2018
Advanced Malignant Solid Neoplasm	Discovery	US	Sumitomo Pharma America, Inc.	10 Jul 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03429218 (AACR2022) Manual	Phase 1	Advanced Malignant Solid Neoplasm	24	TP-0184	(dlghcgmylm) = wawndjmbtw hnoqxesbuj (caztefgmwm ) View more	Positive	15 Jun 2022

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