Delving into the Latest Updates on GSK-3052230 with Synapse

Overview

Basic Info

Drug Type

Antibody fusion proteins

Synonyms

Fibroblast growth factor ligand trap

+ [4]

Target

FGFR1 x FGFR2

Mechanism

FGFR1 antagonists(Fibroblast growth factor receptor 1 antagonists), FGFR2 antagonists(Fibroblast growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsUrogenital DiseasesRespiratory Diseases+ [1]

Active Indication-

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmMalignant Pleural Mesothelioma+ [2]

Originator Organization

Five Prime Therapeutics, Inc.

Active Organization-

Inactive Organization

GSK Plc

Five Prime Therapeutics, Inc.

Human Genome Sciences, Inc.

Drug Highest PhaseSuspendedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 150418

Sequence Code 1117836251

This phase IB trial aims to identify anticancer activity of GSK3052230 in subjects with malignancies with abnormal dependence on FGF pathway signaling. Combination doses of GSK3052230 with standard of care chemotherapy in the first and second line or greater setting of metastatic squamous non-small cell lung cancer (NSCLC) and first line malignant pleural mesothelioma subjects will be studied in the 3+3 dose-escalation design. This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label Phase IB study designed to evaluate the safety, tolerability and preliminary activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin (Arm C). Approximately 70 subjects will be enrolled in the study (approximately up to 120 may be enrolled).

Start Date09 Oct 2013

Sponsor / Collaborator

GSK Plc

NCT01604863

/ SuspendedPhase 1

Multi-Center, Open-Label Phase 1B Study to Evaluate the Safety and Tolerability of HGS1036 in Combination With Paclitaxel and Carboplatin, Cisplatin and Etoposide, or Docetaxel in Subjects With Advanced Solid Malignancies

The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, or docetaxel.

Start Date01 Jun 2012

Sponsor / Collaborator

Human Genome Sciences, Inc.

NCT01244438

/ WithdrawnPhase 2

An Open-Label Phase 2 Pilot Study Evaluating the Activity and Safety of FP 1039 in Subjects With Advanced and/or Recurrent Endometrial Cancers With Specific FGFR2 Mutations

An open-label, non-randomized, single arm study to assess the safety, tolerability, and pharmacokinetics of FP-1039 given by weekly intravenous (IV) administrations in advanced endometrial cancer patients with FGFR2-specific mutations. FP-1039 will be dosed weekly starting at a dose of up to 16 mg/kg.

Start Date01 Jan 2011

Sponsor / Collaborator

Five Prime Therapeutics, Inc.

[+1]

100 Clinical Results associated with GSK-3052230

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100 Translational Medicine associated with GSK-3052230

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100 Patents (Medical) associated with GSK-3052230

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11

Literatures (Medical) associated with GSK-3052230

01 Apr 2020·Investigational New DrugsQ3 · MEDICINE

A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma

Q3 · MEDICINE

Article

Author: Bellovin, David I ; Fennell, Dean A ; López, Pilar Garrido ; Baker-Neblett, Katherine ; DeYoung, M Phillip ; Levchenko, Evgeny ; Trigo, José ; Vasquez, James ; van Brummelen, Emilie M J ; Gadgeel, Shirish ; Kostorov, Vladimir ; Orlov, Sergey ; Vansteenkiste, Johan F ; Morgensztern, Daniel ; Mitrica, Ionel ; Schellens, Jan H M ; Zauderer, Marjorie G ; Yan, Li ; Kindler, Hedy L ; Wang, Xiaowei ; Dómine, Manuel ; Viteri, Santiago

Background Fibroblast growth factors (FGFs) have a fundamental role in cancer. Sequestering FGFs with GSK3052230 (FP-1039) blocks their ability to activate FGFRs while avoiding toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Methods A multicenter, open-label, phase Ib study evaluated weekly GSK3052230 added to pemetrexed/cisplatin in patients with treatment-naive, unresectable malignant pleural mesothelioma. Doses were escalated according to a 3 + 3 design, followed by cohort expansion at the maximum tolerated dose (MTD). Endpoints included safety, overall response rate, progression-free survival, and pharmacokinetics. Results 36 patients were dosed at 10, 15, and 20 mg/kg doses of GSK3052230. Three dose-limiting toxicities were observed at 20 mg/kg and one at 15 mg/kg. The MTD was defined as 15 mg/kg and used for cohort expansion. The most common treatment-related adverse events (AEs) were nausea (56%), decreased appetite (36%), infusion reactions (36%), decreased neutrophil counts (36%), and fatigue (33%). The confirmed ORR was 39% (95% CI: 23.1-56.5) (14/36 PRs) and 47% had stable disease (17/36), giving a disease control rate of 86%. At 15 mg/kg GSK3052230 (n = 25), the ORR was 44% (95% CI: 24.4-65.1), and the median PFS was 7.4 months (95% CI: 6.7-13.4). Four patients had disease control for over 1 year, and three were still ongoing. Conclusion At 15 mg/kg weekly, GSK3052230 was well tolerated in combination with pemetrexed/cisplatin and durable responses were observed. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

01 Oct 2019·Lung CancerQ2 · MEDICINE

An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer

Q2 · MEDICINE

Article

Author: Paik, Paul K ; Delgado, Ignacio ; Garrido, Pilar ; Burdaeva, Olga ; Baker-Neblett, Katherine ; Morgensztern, Daniel ; Shomova, Marina ; Yan, Li ; Vasquez, James ; Karaseva, Nina ; Felip, Enriqueta ; Orlov, Sergey ; Lassen, Ulrik ; Dómine, Manuel ; Mitrica, Ionel ; Trigo, José ; DeYoung, M Phillip ; Lara, Primo ; Wang, Xiaowei

OBJECTIVESGSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients.METHODS AND METHODSEligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m² and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m² in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment.RESULTSTwenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B.CONCLUSIONGSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

18 Jun 2018·International Journal of OphthalmologyQ4 · MEDICINE

Protective effects of a novel drug RC28-E blocking both VEGF and FGF2 on early diabetic rat retina

Q4 · MEDICINE

ArticleOA

Author: Liu, Xun ; Li, Xiao-Rong ; Yu, Guang-Wei ; Zhang, Yan ; Bo, Qi-Yu ; Fang, Jian-Min ; Jiang, Jing ; Yang, Qian-Hui ; Ru, Yu-Sha ; Han, Qian ; Zhang, Xiao-Min ; Huang, Min ; Wang, Ling ; Wu, Mian-Mian

AIMTo investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats.METHODSThe streptozotocin (STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus (DM) group (saline, 3 µL/eye); RC28-E at low (0.33 µg/µL, 3 µL), medium (1 µg/µL, 3 µL), and high (3 µg/µL, 3 µL) dose groups; vascular endothelial growth factor (VEGF) Trap group (1 µg/µL, 3 µL); fibroblast growth factor (FGF) Trap group (1 µg/µL, 3 µL). Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein (GFAP) expression was examined by immunofluorescence. Blood-retinal barrier (BRB) breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy (TEM). Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay (ELISA). The retinal expression of intercellular cell adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction (qPCR).RESULTSTUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap (all P<0.05), the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap (P<0.01). GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina (P<0.01). TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs.CONCLUSIONDual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy (DR).

100 Deals associated with GSK-3052230

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malignant Pleural Mesothelioma	Phase 2	BE	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	RU	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	NL	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	DK	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	ES	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	GB	GSK Plc	09 Oct 2013
Malignant Pleural Mesothelioma	Phase 2	US	GSK Plc	09 Oct 2013
Advanced Malignant Solid Neoplasm	Phase 2	US	Human Genome Sciences, Inc.	01 Jun 2012
Recurrent Endometrial Cancer	Phase 2	-	Five Prime Therapeutics, Inc.	01 Jan 2011
Advanced cancer	Phase 2	US	Five Prime Therapeutics, Inc.	01 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01868022 (Pubmed) Manual	Phase 1	Non-Small Cell Lung Cancer FGFR1 Amplification	29	paclitaxel+carboplatin+GSK3052230	(ugymtvokam) = the MTD was not reached. ckxuozvbcj (aisdvmuzoe ) View more	Positive	01 Oct 2019
				docetaxel+GSK3052230
NCT01868022 (CTgov)	Phase 1	Malignant Pleural Mesothelioma \| Neoplasms \| Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	65	Carboplatin+GSK3052230+Paclitaxel (5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A)	moufknncxj(scslwpyarj) = wtjggdtfzi svxkopkjjr (lxtwmiikpx, slascajlcw - ghopgbaonp) View more	-	11 Feb 2019
				Carboplatin+GSK3052230+Paclitaxel (10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A)	moufknncxj(scslwpyarj) = sbytscikve svxkopkjjr (lxtwmiikpx, tjkgzveouu - wiqpnkpplf) View more
NCT01868022 (ASCO2016)	Phase 1	Malignant Pleural Mesothelioma	24	GSK3052230 + paclitaxel+carboplatin	(dezsddpjvh) = xkmthirehr ppmrxgierj (qtfdrjxulg )	-	20 May 2016
				GSK3052230 + pemetrexed+cisplatin	(dezsddpjvh) = edopqqhnaz ppmrxgierj (qtfdrjxulg )
NCT00687505 (Pubmed \| Ann Oncol) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	39	FP-1039	(mhhwuarrbx) = reported at doses of 0.75 mg/kg (urticaria), 1 mg/kg (intestinal perforation and neutropenia), and 16 mg/kg (muscular weakness). wgwnqabrix (uxqlenparc )	Positive	01 Mar 2016
NCT01868022 (WCLC2015)	Phase 1	Malignant Pleural Mesothelioma \| Squamous non-small cell lung cancer	34	GSK3052230	exkhotvmkv(xgntypbjec) = wwkcablppq hspgbjcpxa (csuusiwgcy )	-	09 Sep 2015