Delving into the Latest Updates on Cediranib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cediranib (USAN/INN), Cediranib-maleate, Recentin

+ [4]

Target

VEGFR1 x VEGFR2 x VEGFR3

Mechanism

VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists), VEGFR3 antagonists(Vascular endothelial growth factor receptor 3 antagonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [5]

Active Indication

Endometrioid carcinoma ovaryFallopian Tube Clear Cell AdenocarcinomaOvarian clear cell adenocarcinoma+ [61]

Inactive Indication

acute leukemiaAcute Lymphoblastic LeukemiaAcute myeloid leukaemia with 11q23 abnormality+ [114]

Originator Organization

AstraZeneca PLC

Active Organization

National Cancer Institute

AstraZeneca PLC

University College London

Inactive Organization

Wyeth AB

AstraZeneca Pharmaceuticals Co. Ltd.

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (EU), Orphan Drug (US)

Login to view timeline

Structure

Molecular FormulaC25H27FN4O3

InChIKeyXXJWYDDUDKYVKI-UHFFFAOYSA-N

CAS Registry288383-20-0

A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior Bevacizumab

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Start Date10 Jun 2021

Sponsor / Collaborator

National Cancer Institute

[+1]

NCT04090567 / RecruitingPhase 2IIT

Overcoming PARP Inhibitor Resistance in BRCA Germline Mutation Positive Advanced Breast Cancer

This phase II trial studies how well olaparib with cediranib or AZD6738 works in treating patients with germline BRCA mutated breast cancer that has spread to other places in the body (advanced or metastatic). Olaparib, cediranib, and AZD6738 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date28 Jul 2020

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT03741426 / RecruitingPhase 2IIT

WIndow of Opportunity Clinical Trials Platform for Evaluation of Novel Treatments Strategies in REnal Cell Cancer

Evaluation of proof of mechanism with relation to ktrans and/or CD8 count when 3 different IMPs are given as monotherapy or as combination therapy. These would be administered in the "window of opportunity", prior to nephrectomy in surgically resectable renal cell cancer

Start Date27 Jul 2020

Sponsor / Collaborator

Cambridge University Hospitals NHS Foundation Trust

[+3]

100 Clinical Results associated with Cediranib

Login to view more data

100 Translational Medicine associated with Cediranib

Login to view more data

100 Patents (Medical) associated with Cediranib

Login to view more data

418

Literatures (Medical) associated with Cediranib

01 Nov 2024·Clinical Lung Cancer

A Phase I Open-Label Study of Cediranib Plus Etoposide and Cisplatin as First-Line Therapy for Patients With Extensive-Stage Small-Cell Lung Cancer or Metastatic Neuroendocrine Non–Small-Cell Lung Cancer

Article

Author: Camidge, D Ross ; Concannon, Kyle F ; Marotti, Marcelo ; Concannon, Kyle F. ; Glisson, Bonnie S. ; Camidge, D. Ross ; Doebele, Robert C. ; Camidge, D.Ross ; Heymach, John V. ; Doebele, Robert C ; Glisson, Bonnie S ; Heymach, John V ; Huang, Chao

INTRODUCTION:

Small cell lung cancer (SCLC) is known to express high levels of the proangiogenic factor vascular endothelial growth factor (VEGF). We assessed the safety and tolerability of cediranib, an oral inhibitor of VEGF receptor tyrosine kinases, in combination with etoposide and cisplatin as first-line therapy for extensive-stage (ES) SCLC or metastatic lung neuroendocrine cancer (NEC).

METHODS:

Patients received up to six 21-day cycles of etoposide (100 mg/m², days 1-3) and cisplatin (80 mg/m², day 1) with once-daily cediranib until disease progression or unacceptable toxicity. Cediranib dosing started at 30 mg with de-escalation cohorts planned based on cycle 1 dose-limiting toxicities (DLTs). An expansion cohort of 12 patients was enrolled at the recommended phase II dose.

RESULTS:

Twenty-two patients (18 with ES SCLC, 4 with NEC) received treatment. Only 4 patients were enrolled at the 30 mg cediranib dose before other studies established 20 mg/day as the recommended dose with chemotherapy. Among the 18 patients enrolled at the 20-mg dose, common adverse events included nausea/vomiting, neutropenia, and diarrhea; 8 patients (44%) had grade 1 or 2 hypertension, and 2 (11%) had grade 3 hemoptysis. For all 18 patients, the objective response rate and median progression-free survival duration were 67% and 7.9 months. Plasma levels of VEGF were significantly higher, and those of soluble VEGFR2 were significantly lower, on day 22 than at baseline but were not correlated with tumor shrinkage.

CONCLUSIONS:

Cediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity.

01 Sep 2024·Clinical Colorectal Cancer

A Phase II, Open-Label, Randomized Trial of Durvalumab With Olaparib or Cediranib in Patients With Mismatch Repair—Proficient Colorectal or Pancreatic Cancer

Article

Author: Han, Ming ; Siu, Lillian L ; Lam, Bernard ; Hernando-Calvo, Alberto ; Avery, Lisa ; Ayodele, Olubukola ; Berman, Hal K ; Pugh, Trevor J ; Bruce, Jeffrey P ; Stayner, Lee-Anne ; Hansen, Aaron R ; Wang, Ben X ; Salawu, Abdulazeez ; Razak, Albiruni R A ; Vila-Casadesús, Maria ; Lungu, Ilinca ; Abbas-Aghababazadeh, Farnoosh ; Vivancos, Ana ; Spreafico, Anna ; Yang, S Y Cindy ; Bedard, Philippe L ; Sanz-Garcia, Enrique ; Haibe-Kains, Benjamin

BACKGROUND:

The use of immunotherapy in mismatch repair proficient colorectal cancer (pMMR-CRC) or pancreatic adenocarcinoma (PDAC) is associated with limited efficacy. DAPPER (NCT03851614) is a phase 2, basket study randomizing patients with pMMR CRC or PDAC to durvalumab with olaparib (durvalumab + olaparib) or durvalumab with cediranib (durvalumab + cediranib).

METHODS:

PDAC or pMMR-CRC patients were randomized to either durvalumab+olaparib (arm A), or durvalumab + cediranib (arm B). Co-primary endpoints included pharmacodynamic immune changes in the tumor microenvironment (TME) and safety. Objective response rate, progression-free survival (PFS) and overall survival (OS) were determined. Paired tumor samples were analyzed by multiplexed immunohistochemistry and RNA-sequencing.

RESULTS:

A total of 31 metastatic pMMR-CRC patients were randomized to arm A (n = 16) or B (n = 15). In 28 evaluable patients, 3 patients had stable disease (SD) (2 patients treated with durvalumab + olaparib and 1 patient treated with durvalumab + cediranib) while 25 had progressive disease (PD). Among patients with PDAC (n = 19), 9 patients were randomized to arm A and 10 patients were randomized to arm B. In 18 evaluable patients, 1 patient had a partial response (unconfirmed) with durvalumab + cediranib, 1 patient had SD with durvalumab + olaparib while 16 had PD. Safety profile was manageable and no grade 4-5 treatment-related adverse events were observed in either arm A or B. No significant changes were observed for CD3+/CD8+ immune infiltration in on-treatment biopsies as compared to baseline for pMMR-CRC and PDAC independent of treatment arms. Increased tumor-infiltrating lymphocytes at baseline, low baseline CD68+ cells and different immune gene expression signatures at baseline were associated with outcomes.

CONCLUSIONS:

In patients with pMMR-CRC or PDAC, durvalumab + olaparib and durvalumab + cediranib showed limited antitumor activity. Different immune components of the TME were associated with treatment outcomes.

01 Aug 2024·GYNECOLOGIC ONCOLOGY

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib

Article

Author: Armstrong, Deborah K ; Xiong, Niya ; Penson, Richard T ; Barry, William T ; Cristea, Mihaela C ; Wenham, Robert M ; Ivy, S Percy ; Chan, Nancy ; Cheng, Su-Chun ; Matulonis, Ursula A ; Olawaiye, Alexander B ; O'Malley, David M ; Matsuo, Koji ; Lee, Jung-Min ; Shapiro, Geoffrey I ; Swisher, Elizabeth M ; Abbruzzese, James L ; Wahner-Hendrickson, Andrea ; Kohn, Elise C ; Liu, Joyce F ; Polak, Madeline

OBJECTIVE:

Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD).

METHODS:

Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity.

RESULTS:

In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23).

CONCLUSIONS:

Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

100 Deals associated with Cediranib

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D08881	Cediranib	L01XE32	DB04849

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Cancer	NDA/BLA	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Ovarian Serous Adenocarcinoma	Phase 3	US	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	JP	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	CA	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	PR	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	KR	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	US	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	JP	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	CA	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	PR	National Cancer Institute	03 May 2016

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01391962 (CTgov)	Phase 2	Alveolar Soft Part Sarcoma	34	AZD2171 (Cediranib) (AZD2171 (Cediranib) 30 mg)	fnvsvkzhto(ciydukhtfh) = nbwxnfjrxp emfmzqeohq (kbkvmazjkn, anrmnyozmp - hvdtoedunv) View more	-	19 Sep 2024
				AZD2171 (Cediranib)+Sunitinib Malate (AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg)	fnvsvkzhto(ciydukhtfh) = hymvyhkmhn emfmzqeohq (kbkvmazjkn, lirwgzkkrp - hfmonejdfu) View more
407 (ESGO2024)	Phase 2	Recurrent Endometrial Cancer	124	Weekly paclitaxel	dulmykjmrt(xboykcyhee) = mhmbccofod tsqytnswzm (syxbzyqdui ) View more	-	10 Mar 2024
				Weekly paclitaxel + Cediranib	dulmykjmrt(xboykcyhee) = ayekviumle tsqytnswzm (syxbzyqdui ) View more
NCT02446600 (NRG-GY004, ESMO2023)	Phase 3	Platinum-Sensitive Primary Peritoneal Carcinoma \| Ovarian Serous Tumor \| Fallopian Tube Clear Cell Adenocarcinoma ... View more	565	cediranib (Standard of care (SOC))	nmfiasgbpd(hhifvhrdng) = zlrbsiujel fwoecrpdhq (uqeapiapoe )	Negative	22 Oct 2023
				Olaparib (O)	nmfiasgbpd(hhifvhrdng) = mnkejqxqdp fwoecrpdhq (uqeapiapoe )
NCT03851614 (DAPPER, ASCO2023)	Phase 2	Leiomyosarcoma	-	Durvalumab plus Cediranib	tftzvhbmfq(govuecqela) = lpgotexfyy vaiqewrbhb (evrobemcew, 10.7 - NR) View more	-	31 May 2023
ESGO2022	Phase 2	Platinum-Resistant Ovarian Carcinoma	30	Cediranib + Paclitaxel	ybjkfnlblr(jdkakfswke) = Three participants had grade 3+ SAEs causally related to cediranib+/-olaparib (one diarrhoea; one diarrhoea and TIA; one vomiting) svjhbfvwtj (tvhertyauc )	Negative	20 Oct 2022
NCT02893917 (National Cancer Institute 9984, Pubmed \| J Clin Oncol)	Phase 2	Metastatic castration-resistant prostate cancer	90	Cediranib 30 mg + Olaparib 200 mg	(ufdvchdvns) = mozacowtmi fnitlixhqq (zefuwnagkp, 5.4 - 12.0) View more	Positive	18 Oct 2022
				Olaparib 300 mg	(ufdvchdvns) = heifoaaewe fnitlixhqq (zefuwnagkp, 3.2 - 8.5) View more
NCT01391962 (AACR2022) Manual	Phase 2	Alveolar Soft Part Sarcoma	34	cediranib	bmlounfogq(pnquyiywad) = wxormmcppi waykjomjzv (rbtcuxqlku ) View more	Negative	15 Jun 2022
				sunitinib	bmlounfogq(pnquyiywad) = mtgxqerakn waykjomjzv (rbtcuxqlku ) View more
NCT02446600 (NRG-GY004, Pubmed \| J Urol)	Phase 3	Platinum-Sensitive Ovarian Carcinoma	565	Platinum-based chemotherapy	(uloecqwzyi) = cvojikzkig ezonnhswjg (nalupuzhdh, 8.7 - 11.2)	Negative	15 Mar 2022
				Olaparib	(uloecqwzyi) = rftevygpkf ezonnhswjg (nalupuzhdh, 6.6 - 8.7)
NCT02446600 (NRG-GY004, ESMO2021)	Phase 3	Platinum-Sensitive Ovarian Carcinoma	565	Olaparib	pbbrgcscbr(mtxdgmfkyd) = ppblmjezgx jqxvqmaaiv (uifuywtotj )	-	19 Sep 2021
				Cediranib and Olaparib	pbbrgcscbr(mtxdgmfkyd) = vhxiijmjez jqxvqmaaiv (uifuywtotj )
NCT01208051 (CTgov)	Phase 1/2	Advanced Thyroid Gland Carcinoma \| Refractory Thyroid Gland Carcinoma \| Refractory Differentiated Thyroid Gland Carcinoma	127	Lenalidomide+Cediranib (Phase I Dose Level 0)	iyzhcoeefs(pozokyzjfo) = vnpqzohtss sxlsjlhdvq (wvnmjgvqij, truknfzztw - nbblxhszkk) View more	-	15 Jul 2021
				Lenalidomide+Cediranib (Phase I Dose Level +1)	iyzhcoeefs(pozokyzjfo) = ozdwiazcmj sxlsjlhdvq (wvnmjgvqij, egmovogfqc - kynciwfeky) View more