Delving into the Latest Updates on CEP-9722 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

PARP1 inhibitors(Poly (ADP-Ribose) polymerase 1 inhibitors), PARP2 inhibitors(Poly (ADP-Ribose) Polymerase 2 inhibitors)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseRespiratory Diseases+ [3]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmMantle-Cell LymphomaNon-Small Cell Lung Cancer+ [2]

Originator Organization

Teva Pharmaceutical Industries Ltd.

Active Organization-

Inactive Organization

Cephalon, Inc.

Checkpoint Therapeutics, Inc.

Teva Pharmaceutical Industries Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC24H26N4O3

InChIKeyCTLOSZHDGZLOQE-UHFFFAOYSA-N

CAS Registry916574-83-9

CEP-9722 is an inhibitor of poly-adenosine diphosphate (ADP) ribose polymerase -1 and -2 (PARP). The primary purpose of this study is to (Part 1) determine the maximum tolerated dose (MTD) of CEP-9722 administered daily to participants with advanced or metastatic solid tumors, (Part 2) to evaluate the safety and tolerability of that dose, and to investigate whether CEP-9722 has antitumor activity as a single agent.

Start Date02 May 2011

Sponsor / Collaborator

Teva Branded Pharmaceutical Products R&D, Inc.

NCT01345357 / CompletedPhase 1

A Dose-Escalation Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP 1 and PARP 2 Inhibitor) in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma

The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.

Start Date01 May 2011

Sponsor / Collaborator

Cephalon, Inc.

NCT00920595 / CompletedPhase 1

An Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP-1 and PARP-2 Inhibitor) as Single-Agent Therapy and as Combination Therapy With Temozolomide in Patients With Advanced Solid Tumors

An open-label study to evaluate the safety, pharmacokinetics, and pharmacodynamics of CEP-9722 as single-agent therapy and as combination therapy with temozolomide in patients with advanced solid tumors.

Start Date01 Jun 2009

Sponsor / Collaborator

Cephalon, Inc.

100 Clinical Results associated with CEP-9722

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100 Translational Medicine associated with CEP-9722

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100 Patents (Medical) associated with CEP-9722

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10

Literatures (Medical) associated with CEP-9722

11 May 2023·BMC pulmonary medicine

The combination therapy of isomucronulatol 7-O-beta-glucoside (IMG) and CEP-9722 targeting ferroptosis-related biomarkers in non-small cell lung cancer (NSCLC)

Article

Author: Liu, Chao ; Cui, Xiaofei ; Bai, Yu ; Liu, Chang ; Dong, Penghua

BACKGROUNDNSCLC is a malignant tumor with a high incidence. Ferroptosis presents an essential function in regulating carcinogenesis and tumor progression. However, the ferroptosis-associated prognostic model based on single-cell sequencing of NSCLC remains unexplored. Our study aims to establish a potential predictive model for NSCLC patients and provide available targeted drugs for clinical treatment.METHODSThe data on NSCLC patients were collected from TCGA and GEO databases to analyze their gene expression profiles. ConsensusCluster was adopted to divide the patients into different groups based on ferroptosis-related genes. Then, the univariable Cox and LASSO analyses were applied to data analysis and model establishment. Single-cell analysis was used to explore the risk score genes in different cell populations and states. The protein levels of these genes were also investigated through the HPA database. Drug sensitivity was evaluated in CellMiner database. CCK8 and colony formation assays were performed to validate potential drugs' effects on lung cancer cell lines.RESULTSA ferroptosis-related prognostic model involving 14 genes in NSCLC patients was established. The risk score model was developed in training set GSE31210 and validated in the test set TCGA. The low-risk score group showed a better prognosis than the high-risk score group. The single-cell analysis revealed that the risk score genes were mainly derived from lung tumor cells. Most risk score genes were more highly expressed in tumor tissue than in normal tissue, according to the HPA database. Besides, these genes were associated with 106 drugs in CellMiner database. Finally, the drug effects on NSCLC cell growth were evaluated by cck8 and colony formation.CONCLUSIONSWe identified an effective ferroptosis-related prognostic model based on single-cell sequencing. The potential prediction model is devoted to exploring clinical therapeutic targets for NSCLC.

01 Dec 2018·Current Treatment Options in OncologyQ2 · MEDICINE

Using PARP Inhibitors in the Treatment of Patients With Ovarian Cancer

Q2 · MEDICINE

Review

Author: Kurnit, Katherine C ; Westin, Shannon N ; Coleman, Robert L

OPINION STATEMENTUse of poly(ADP-ribose) polymerase (PARP) inhibitors has greatly increased over the past 5 years. With several new Food and Drug Administration (FDA) approvals, three PARP inhibitors have entered into standard of care treatment for epithelial ovarian cancer (including ovarian, fallopian tube, and primary peritoneal cancer). Olaparib and rucaparib currently have indications for treatment of recurrent BRCA mutant ovarian cancer. Olaparib, rucaparib, and niraparib all have indications for maintenance therapy in recurrent platinum-sensitive ovarian cancer after response to platinum-based therapy. In our practice, we use both olaparib and rucaparib in the recurrent setting, and all three PARP inhibitors in the maintenance setting. Choice of which PARP inhibitor to use in either setting is largely based upon baseline laboratory values, number of prior therapies, and presence of a BRCA mutation and/or homologous recombination deficiency (HRD). As (HRD) and other biomarker assessments continue to improve, we anticipate being able to better identify which patients might most benefit from PARP inhibitor therapy in the future. The clinically available PARP inhibitors are currently undergoing extensive investigations in clinical trials. Other newer agents such as talazoparib, veliparib, 2X-121, and CEP-9722 are in earlier stages of development. As more FDA-approved indications for PARP inhibitor therapy in ovarian cancer become available, we anticipate the decision of which PARP inhibitor to use will become increasingly complex.

01 Apr 2016·Anti-Cancer DrugsQ4 · MEDICINE

An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors

Q4 · MEDICINE

Article

Author: Gombos, Andrea ; Soria, Jean-Charles ; Campone, Mario ; Bahleda, Rastilav ; Frenel, Jean-Sebastien ; Bourbouloux, Emmanuelle ; Aftimos, Philippe ; Awada, Ahmad ; Varga, Andrea

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors may potentiate chemotherapy by hindering DNA damage repair pathways. CEP-9722 is the prodrug of CEP-8983, a selective inhibitor of PARP-1 and PARP-2. Preclinical studies and a prior phase 1 study suggested that CEP-9722 may cause less myelosuppression than has been observed with other oral PARP inhibitors. The primary objective of this study was to determine the maximum-tolerated dose of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors. All patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle. Patients who completed one cycle of chemotherapy alone continued chemotherapy in combination with CEP-9722 150, 200, 300, or 400 mg orally twice daily on days 2-7, with dose-limiting toxicity assessed in cycle 2. Patients experiencing clinical benefit could continue treatment until disease progression or unacceptable toxicity. Thirty-two patients enrolled; 18 patients completed cycle 1 and received chemotherapy plus CEP-9722. The median (range) treatment administration with CEP-9722 was five (1-12) cycles. No patient experienced dose-limiting toxicity with CEP-9722 treatment. Grade 3/4 hematologic adverse events included neutropenia (28%) and leukopenia (11%); adverse events led to discontinuation in 33% of patients. One patient achieved complete response, three had partial responses, and 11 had stable disease; however, the relative contribution of CEP-9722 and/or the chemotherapeutic agents cannot be determined from this single-arm design. This study was discontinued before determination of the maximum-tolerated dose because of highly variable CEP-8983 exposure in all cohorts and toxicity, particularly chemotherapy-induced myelosuppression.

100 Deals associated with CEP-9722

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14882

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 2	US	Checkpoint Therapeutics, Inc.	29 Sep 2013
Mantle-Cell Lymphoma	Phase 2	BE	Cephalon, Inc.	01 May 2011
Mantle-Cell Lymphoma	Phase 2	FR	Cephalon, Inc.	01 May 2011
Advanced Malignant Solid Neoplasm	Phase 2	GB	Cephalon, Inc.	01 Jun 2009
Advanced Malignant Solid Neoplasm	Phase 2	FR	Cephalon, Inc.	01 Jun 2009
Non-Small Cell Lung Cancer	Phase 2	US	Cephalon, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	US	Cephalon, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	-	Teva Pharmaceutical Industries Ltd.	-
Non-Small Cell Lung Cancer	Phase 2	-	Teva Pharmaceutical Industries Ltd.	-
Ovarian Cancer	Phase 2	-	Teva Pharmaceutical Industries Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01311713 (CTgov)	Phase 1/2	Metastatic Solid Tumor	45	CEP-9722 (CEP-9722 Dose 1 QD)	qkaoacijlm(vrjzelxocb) = ytklachbhu ijkuludojm (ukfdckvety, dfsukngkmd - ukjwtggatg) View more	-	30 Jan 2024
				CEP-9722 (CEP-9722 Dose 1 BID)	qkaoacijlm(vrjzelxocb) = wptqssjenc ijkuludojm (ukfdckvety, pkbzxkdyoz - wfsczrwefh) View more