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

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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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6

Literatures (Medical) associated with BCL-201

01 Oct 2021·Medical HypothesesQ4 · MEDICINE

Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study

Q4 · MEDICINE

Article

Author: Oh, Ki Kwang ; Adnan, Md ; Cho, Dong Ha

Currently, a plethora of information has been accumulated concerning COVID-19, including the transmission pathway of SARs-CoV-2. Thus, we retrieved targets associated with the development of COVID-19 via PubChem. A total of 517 targets were identified, and signaling pathways responded after infection of SARs-CoV-2 in humans constructed a bubble chart using RPackage. The bubble chart result suggested that the key signaling pathway against COVID-19 was the estrogen signaling pathway associated with AKT1, HSP90AB1, BCL2 targets. The three targets have the strongest affinity with three ligands-Akti-1/2, HSP990, S55746, respectively. In conclusion, this work provides three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells.

01 Dec 2020·Investigational New DrugsQ3 · MEDICINE

Translational approach from preclinical to clinical: comparison of dose finding methods of a new Bcl2 inhibitor using PK-PD modeling and interspecies extrapolation

Q3 · MEDICINE

Article

Author: Henin, Emilie ; Ogier, Julien ; Kraus-Berthier, Laurence ; Pierrillas, Philippe B ; Bouzom, François ; Amiel, Magali ; Tod, Michel ; Chenel, Marylore

The attrition rate of anticancer drugs during the clinical development remains very high. Interspecies extrapolation of anticancer drug pharmacodynamics (PD) could help to bridge the gap between preclinical and clinical settings and to improve drug development. Indeed, when combined with a physiologically-based-pharmacokinetics (PBPK) approach, PD interspecies extrapolation could be a powerful tool for predicting drug behavior in clinical trials. The present study aimed to explore this field for anticipating the clinical efficacy of a new Bcl-2 inhibitor, S 55746, for which dose ranging studies in xenografted mice and clinical data from a phase 1 trial involving cancer patients were available. Different strategies based on empirical or more mechanistic assumptions (based on PBPK-PD modelling) were developped and compared: the Rocchetti approach (ROC); the Orthogonal Rocchetti approach (oROC), a variant of ROC based on an orthogonal regression; the Consistent across species approach, bringing out an efficacy parameter assumed to be consistent across species; and the Scaling species-specific parameters approach, assuming the concentration-efficacy link is the same in mice as in humans, after allometric scaling. Empirical approaches (ROC and oROC) gave similar predictive performances and seemed to overestimate the active S 55746 dose compared to mechanistic approaches, while strategies elaborated from semi-mechanistic concepts and PBPK-PD modelling did not seem to be invalidated by clinical efficacy data. Also, empirical methods only predict a single dose level for the subsequent clinical studies, whereas mechanism-based strategies are more informative about the dose response relationship, highlighting the potential interest of such approaches in drug development.

23 Jun 2020·Blood AdvancesQ2 · MEDICINE

Cotargeting BCL-2 and MCL-1 in high-risk B-ALL

Q2 · MEDICINE

Article

Author: Geneste, Olivier ; Chanrion, Maïa ; Litalien, Veronique ; Schoumacher, Marie ; Moujalled, Donia M. ; Roberts, Andrew W. ; Kraus-Berthier, Laurence ; Georgiou, Angela ; Hediyeh-zadeh, Soroor ; Davis, Melissa J. ; Brown, Lauren ; Wei, Andrew ; Maragno, Ana-Leticia ; Hanna, Diane T. ; Huang, David C. S. ; Lessene, Guillaume ; Rasmussen, Lorna ; Khaw, Seong L. ; Mullighan, Charles G. ; Fleming, Shaun ; Bartolo, Ray ; Ekert, Paul G. ; Ng, Ashley P. ; Banquet, Sébastien ; White, Christine A. ; Pomilio, Giovanna

AbstractImproving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option. We report that combined targeting of BCL-2 and MCL1 is synergistic in B-ALL in vitro. The combination demonstrated greater efficacy than standard chemotherapeutics and TKIs in primary samples from adult B-ALL with Ph+ ALL, Ph-like ALL, and other B-ALL. Moreover, combined BCL-2 or MCL1 inhibition with dasatinib showed potent killing in primary Ph+ B-ALL cases, but the BH3-mimetic combination appeared superior in vitro in a variety of Ph-like ALL samples. In PDX models, combined BCL-2 and MCL1 targeting eradicated ALL from Ph− and Ph+ B-ALL cases, although fatal tumor lysis was observed in some instances of high tumor burden. We conclude that a dual BH3-mimetic approach is highly effective in diverse models of high-risk human B-ALL and warrants assessment in clinical trials that incorporate tumor lysis precautions.

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
Recurrent Chronic Lymphoid Leukemia	Phase 2	SG	Institut de Recherches Intern Servier	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Phase 2	PL	Institut de Recherches Intern Servier	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Phase 2	FR	Institut de Recherches Intern Servier	01 Mar 2014
Recurrent Chronic Lymphoid Leukemia	Phase 2	KR	Institut de Recherches Intern Servier	01 Mar 2014
Chronic Lymphocytic Leukemia	Phase 1	-	Ligand UK Ltd.	-
Chronic Lymphocytic Leukemia	Phase 1	-	Novartis Pharma AG	-
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	-

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


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