Delving into the Latest Updates on BCL-201 with Synapse

This is a phase Ib multi-center, open-label study: escalation part followed by expansion part. The primary purpose of the Phase Ib CBCL201X2102C study is to characterize the safety and tolerability of BCL201 combined with idelalisib in patients with FL and MCL.
Approximately 65 patients are to be enrolled.
The primary endpoint for the Phase Ib is frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as ECG changes. An adaptive Bayesian logistic regression model (BLRM) will guide the dose escalation to determine the MTD/RDE in phase Ib. In addition Bayesian regression models will be used to estimate the dose-exposure relationships for both BCL201 and idelalisib in order to guide the escalation steps. A Bayesian method for the expansion part will be used for the primary activity objective.
The study data will be analyzed and reported based on all patients' data of the escalation and expansion part.

Start Date16 Nov 2015

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT02920541

/ CompletedPhase 1IIT

Phase I Dose-escalation Study of the Orally Administered Selective Bcl-2 Inhibitor S 055746 as Monotherapy for the Treatment of Patients With Acute Myeloid Leukaemia (AML) or High or Very High Risk Myelodysplastic Syndrome (MDS)

The purpose of this study is to determine the safety profile and tolerability of S 055746 in patients with AML, and high or very high risk MDS, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD profile and preliminary efficacy.

Start Date01 Jan 2015

Sponsor / Collaborator

Institut de Recherches Intern Servier

[+1]

NCT02920697

/ CompletedPhase 1IIT

Phase I Dose-escalation Study of Oral Administration of the Selective Bcl2 Inhibitor S 55746 in Patients With Refractory or Relapsed Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma

The purpose of this study is to determine the safety profile and tolerability of S 55746 in patients with CLL, B-Cell NHL and MM, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD profile and preliminary efficacy.

Start Date01 Mar 2014

Sponsor / Collaborator

Institut de Recherches Intern Servier

[+1]

100 Clinical Results associated with BCL-201

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100 Translational Medicine associated with BCL-201

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100 Patents (Medical) associated with BCL-201

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20

Literatures (Medical) associated with BCL-201

01 Apr 2024·Haematologica

BH3 profiling as pharmacodynamic biomarker for the activity of BH3 mimetics.

Letter

Author: Pan, Rongqing Aaron ; Ryan, Jeremy ; Halilovic, Ensar ; Qiu, Shumei ; Wang, Youzhen ; Letai, Anthony ; Villalobos-Ortiz, Mariana ; Morris, Erick

Not available.

19 Mar 2024·Cancer Research Communications

Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Article

Author: Varghese, Diana Grace ; Hoang, Chuong D. ; Sun, Nai-Yun ; McKnight, Crystal ; Del Rivero, Jaydira ; Hernandez, Jonathan M. ; Elloumi, Fathi ; Beck, Erin ; Roper, Nitin ; Zhang, Xiaohu ; Wilson, Kelli M. ; Travers, Jameson ; Klumpp-Thomas, Carleen ; Holland, David O. ; Jo, Ukhyun ; Ceribelli, Michele ; Itkin, Zina ; Pommier, Yves ; Takebe, Naoko ; Thomas, Craig J. ; Kumar, Suresh ; Arakawa, Yasuhiro ; Thomas, Anish

AbstractCurrent treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed to identify novel therapeutic options for ACC. An extensive drug screen was conducted to identify compounds with potential activity against ACC cell lines. We further investigated the mechanism of action of the identified compound, TAK-243, its synergistic effects with current ACC therapeutics, and its efficacy in ACC models including patient-derived organoids and mouse xenografts. TAK-243, a clinical ubiquitin-activating enzyme (UAE) inhibitor, showed potent activity in ACC cell lines. TAK-243 inhibited protein ubiquitination in ACC cells, leading to the accumulation of free ubiquitin, activation of the unfolded protein response, and induction of apoptosis. TAK-243 was found to be effluxed out of cells by MDR1, a drug efflux pump, and did not require Schlafen 11 (SLFN11) expression for its activity. Combination of TAK-243 with current ACC therapies (e.g., mitotane, etoposide, cisplatin) produced synergistic or additive effects. In addition, TAK-243 was highly synergistic with BCL2 inhibitors (Navitoclax and Venetoclax) in preclinical ACC models including patient-derived organoids. The tumor suppressive effects of TAK-243 and its synergistic effects with Venetoclax were further confirmed in a mouse xenograft model. These findings provide preclinical evidence to support the initiation of a clinical trial of TAK-243 in patients with advanced-stage ACC. TAK-243 is a promising potential treatment option for ACC, either as monotherapy or in combination with existing therapies or BCL2 inhibitors.Significance:ACC is a rare endocrine cancer with poor prognosis and limited therapeutic options. We report that TAK-243 is active alone and in combination with currently used therapies and with BCL2 and mTOR inhibitors in ACC preclinical models. Our results suggest implementation of TAK-243 in clinical trials for patients with advanced and metastatic ACC.

09 Feb 2023·Blood

Acquired BAX mutations in AML

Communications

Author: Kim, Won Jun ; Abdel-Wahab, Omar

A review.In this issue of Blood, Moujalled et al1 identify loss-of-function BAX mutations in 17% of patients with acute myeloid leukemia (AML), relapsing after treatment with the BH3-mimetic venetoclax, providing a novel explanation for venetoclax resistance in AML.

100 Deals associated with BCL-201

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Phase 1	-	Novartis Pharma AG	-
Chronic Lymphocytic Leukemia	Phase 1	-	Ligand UK Ltd.	-
Follicular Lymphoma	Phase 1	-	Les Laboratoires Servier SAS	-
Follicular Lymphoma	Phase 1	-	Ligand UK Ltd.	-
Mantle-Cell Lymphoma	Phase 1	-	Ligand UK Ltd.	-
Mantle-Cell Lymphoma	Phase 1	-	Les Laboratoires Servier SAS	-
Recurrent Chronic Lymphoid Leukemia	Discovery	South Korea	Institut de Recherches Intern Servier	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Discovery	Singapore	Adir SRL	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Discovery	Germany	Adir SRL	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Discovery	South Korea	Adir SRL	01 Mar 2014

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02920697 (Literature \| ICML2017) Manual	Phase 1	Non-Hodgkin's lymphoma refractory \| Recurrent Non-Hodgkin Lymphoma	37	S55746	(rnmjohqril) = lymphopenia (n = 4), anemia (n = 3), and disease progression (n = 3) wqwjhmcsej (fxlgbgnckw ) View more	Positive	07 Jun 2017
NCT02920541 (EUDRACT 2014-002559-24, EHA2017)	Phase 1	Acute Myeloid Leukemia \| High Risk Myelodysplastic Syndrome	34	S55746/BCL201	(scrycbgade) = 2 pts sxmgaaxlvq (vtkkqeyysw ) View more	Positive	18 May 2017