Delving into the Latest Updates on GSK-2636771 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

GPR39 x PI3Kβ

Action

agonists, inhibitors

Mechanism

GPR39 agonists(G protein-coupled receptor 39 agonists), PI3Kβ inhibitors(Phosphatidylinositol 3 kinase beta inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

NeoplasmsMetastatic melanoma

Inactive Indication

Advanced Malignant Solid NeoplasmMetastatic castration-resistant prostate cancerProstatic Cancer+ [1]

Originator Organization

GSK Plc

Active Organization

GSK Plc

Merck Sharp & Dohme Corp.

Inactive Organization

Yonsei University Health System

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H22F3N3O3

InChIKeyXTKLTGBKIDQGQL-UHFFFAOYSA-N

CAS Registry1372540-25-4

The goal of this clinical research study is to learn if GSK2636771 given in combination with pembrolizumab can help to control the disease in patients with refractory (has not responded to treatment) metastatic melanoma. The safety of this drug combination will also be studied.
This is an investigational study. Pembrolizumab is FDA approved and commercially available and FDA approved for the treatment of several types of cancer, including melanoma. GSK2636771 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.
Up to 41 participants will be enrolled in this study. All will take part at MD Anderson.

Start Date17 Jul 2017

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+4]

NCT04439149

/ Active, not recruitingPhase 2IIT

MATCH Treatment Subprotocol N: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Mutation or Deletion, With PTEN Expression on IHC

This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a genetic change called PTEN mutation or deletion. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells that express PTEN mutations. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth.

Start Date25 Feb 2016

Sponsor / Collaborator

National Cancer Institute

NCT04439188

/ Active, not recruitingPhase 2IIT

MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Loss by IHC

This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a complete loss of PTEN expression. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells with complete loss of PTEN expression. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth.

Start Date25 Feb 2016

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with GSK-2636771

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100 Translational Medicine associated with GSK-2636771

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100 Patents (Medical) associated with GSK-2636771

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18

Literatures (Medical) associated with GSK-2636771

20 Jan 2024·Journal of Clinical Oncology

Open-Label, Multicenter, Randomized, Biomarker-Integrated Umbrella Trial for Second-Line Treatment of Advanced Gastric Cancer: K-Umbrella Gastric Cancer Study

Article

Author: Lee, Choong-Kun ; Park, Sook Ryun ; Zang, Dae Young ; Nam, Chung Mo ; Rha, Sun Young ; Hwang, In Gyu ; Chung, Hyun Cheol ; Jung, Minkyu ; Kim, Hyo Song ; Kim, Hyunki ; Koo, Dong-Hoe ; Bae, Woo Kyun ; Jeung, Hei Cheul ; Lee, Hyun Woo ; Park, Sejung

PURPOSE This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC). PATIENTS AND METHODS Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cβ inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti–PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus–related cases (nivolumab; NIVO cohort). NONE cohort in the biomarker group without predefined biomarkers and control group received SOC (paclitaxel with or without ramucirumab). The primary end point was progression-free survival (PFS), and the secondary end points were efficacy and safety. RESULTS A total of 318 patients were randomly assigned into the control (n = 64) and biomarker (n = 254; EGFR, n = 67; PTEN, n = 37; NIVO, n = 48; NONE, n = 102) groups. Median follow-up was 35 months. Median PFS and overall survival (OS) were 3.7 (95% CI, 3.1 to 4.1) and 8.6 (95% CI, 7.6 to 9.8) months in the biomarker group and 4.0 (95% CI, 3.0 to 4.6) and 8.7 (95% CI, 7.1 to 9.9) months in the control group. Afatinib addition led to marginal survival benefits to patients with EGFR 3+ compared with SOC (PFS, 4.0 v 2.2 months; P = .09), but GSK2636771 did not prolong the survival of patients with PTEN loss. Addition of nivolumab showed a durable survival benefit (median OS, 12.0 v 7.6 months; P = .08). CONCLUSION Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents.

01 May 2022·Advanced Healthcare MaterialsQ2 · MATERIALS SCIENCE

Arming Immune Cell Therapeutics with Polymeric Prodrugs

Q2 · MATERIALS SCIENCE

Article

Author: Srinivasan, Selvi ; Blumenthal, Ian ; Crane, Courtney A. ; Chiefari, John ; Stayton, Patrick S. ; Huang, Fei ; Roy, Debashish ; Montgomery, Kate S. ; Gardell, Jennifer L. ; Kreuser, Shannon A. ; Brempelis, Katherine J. ; Matthaei, James F. ; López, Ciana L. ; Jensen, Michael C.

AbstractEngineered immune cells are an exciting therapeutic modality, which survey and attack tumors. Backpacking strategies exploit cell targeting capabilities for delivery of drugs to combat tumors and their immune‐suppressive environments. Here, a new platform for arming cell therapeutics through dual receptor and polymeric prodrug engineering is developed. Macrophage and T cell therapeutics are engineered to express a bioorthogonal single chain variable fragment receptor. The receptor binds a fluorescein ligand that directs cell loading with ligand‐tagged polymeric prodrugs, termed “drugamers.” The fluorescein ligand facilitates stable binding of drugamer to engineered macrophages over 10 days with 80% surface retention. Drugamers also incorporate prodrug monomers of the phosphoinositide‐3‐kinase inhibitor, PI‐103. The extended release of PI‐103 from the drugamer sustains antiproliferative activity against a glioblastoma cell line compared to the parent drug. The versatility and modularity of this cell arming system is demonstrated by loading T cells with a second fluorescein‐drugamer. This drugamer incorporates a small molecule estrogen analog, CMP8, which stabilizes a degron‐tagged transgene to provide temporal regulation of protein activity in engineered T cells. These results demonstrate that this bioorthogonal receptor and drugamer system can be used to arm multiple immune cell classes with both antitumor and transgene‐activating small molecule prodrugs.

01 Oct 2021·Clinical Cancer ResearchQ1 · MEDICINE

A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer

Q1 · MEDICINE

Article

Author: Gorczyca, Michele ; Vaishampayan, Ulka N. ; Henson, Lynn ; Dorff, Tanya B. ; Tolson, Jerry ; Roy-Ghanta, Sumita ; Pantuck, Allan J. ; de Bono, Johann S. ; York, Whitney ; Sarker, Debashis ; Ganji, Gopinath ; Aparicio, Ana M. ; Vasist, Lakshmi ; Dawson, Nancy A.

AbstractPurpose:In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance.Patients and Methods:In this phase I study (NCT02215096), patients with PTEN-deficient mCRPC who progressed on prior enzalutamide received once-daily enzalutamide 160 mg plus PI3Kβ inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100-mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended phase II dose, and assess the 12-week non-progressive disease (PD) rate.Results:Overall, 37 patients were enrolled; 36 received ≥1 dose of GSK2636771 (200 mg: n = 22; 300 mg: n = 12; 400 mg: n = 2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n = 1; 300 mg: n = 2, 400 mg: n = 2). No new or unexpected adverse events or evidence of drug–drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% confidence interval: 28.2–71.8, n = 22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. Four of 34 (12%) patients had prostate-specific antigen reduction of ≥50%.Conclusions:Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.

100 Deals associated with GSK-2636771

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11795

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 2	United States	Merck Sharp & Dohme Corp.	17 Jul 2017
Metastatic melanoma	Phase 2	United States	GSK Plc	17 Jul 2017
Neoplasms	Phase 2	-	GSK Plc	-
Prostatic Cancer	Preclinical	United Kingdom	GSK Plc	-
Prostatic Cancer	Preclinical	United States	GSK Plc	-
Stomach Cancer	Discovery	South Korea	Yonsei University Health System	10 Jan 2016
Metastatic castration-resistant prostate cancer	Discovery	United Kingdom	GSK Plc	13 Nov 2014
Advanced Malignant Solid Neoplasm	Discovery	United States	GSK Plc	10 Nov 2011
Advanced Malignant Solid Neoplasm	Discovery	South Korea	GSK Plc	10 Nov 2011
Advanced Malignant Solid Neoplasm	Discovery	United Kingdom	GSK Plc	10 Nov 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02951091 (ASCO2022) Manual	Phase 2	Advanced Gastric Adenocarcinoma Second line	329	biomarker group	(ewdzrzgvsz) = rnqydpifmh kqnvzjvefe (iarxunryss, 3.2 - 4.3) View more	Negative	02 Jun 2022
				paclitaxel+afatinib (EGFR 2+/3+ patients)	(ewdzrzgvsz) = dexrczrhqq kqnvzjvefe (iarxunryss, 3.3 - 4.6) View more
NCT01458067 (ASCO2022) Manual	Phase 1/2	Metastatic castration-resistant prostate cancer	12	GSK2636771+pembrolizumab	(xkhudejhzg) = The RP2D was identified at 200mg PO QD of GSK2636771 + pembrolizumab 200mg IV Q3W. pvuwjpuynj (pgygwfzsvi ) View more	Positive	02 Jun 2022
NCT02951091 \| NCT02615730 (ASCO_GI2022)	Phase 2	Advanced Gastric Adenocarcinoma Second line PI3K/Akt pathway alterations \| EBV-related \| dMMR/MSI-H ... View more	54	GSK2636771	(uwyihrfbta) = xergnkozvq nkrommartf (rxispjkdyy ) View more	-	19 Jan 2022
				Paclitaxel	(uwyihrfbta) = aqhgbkqnpo nkrommartf (rxispjkdyy ) View more
NCT01458067 (ESMO 12021 \| ESMO 22021) Manual	Phase 1/2	HR-positive/HER2-low Solid Tumors \| Melanoma	27	GSK2636771+pembrolizumab	(virjoxkcvh) = G771 (200 mg PO QD) fbyqmrhufk (umumdkmoqo ) View more	Positive	16 Sep 2021
NCT02215096 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Metastatic castration-resistant prostate cancer	37	enzalutamide+GSK2636771	zioguhxhqf(gkhqmpttxj) = gwzbwqzglm isiflfefax (ddmsvvzhfs, 28.2 - 71.8) View more	Negative	19 Jul 2021
NCT02615730 (SO-10, ESMO_GI2021)	Phase 1/2	Advanced gastric carcinoma PTEN expression	42	GSK2636771 300mg once daily + paclitaxel 80mg/m2	(exrbgwyoua) = vmbwcupswu hitverrhbv (mrufamyeku, 11.1 - 13.2) View more	-	03 Jul 2021
				GSK2636771 200mg once daily + paclitaxel 80mg/m2	(exrbgwyoua) = hgpqbqjkkp hitverrhbv (mrufamyeku, 26.2 - 40.7) View more
NCT02215096 (CTgov)	Phase 1	Metastatic castration-resistant prostate cancer	37	Enzalutamide (Enzalutamide Only (run-in Period))	kcfdmgbcdf(oaxwloazvn) = ezrpgclcwe lfkcxzqwcb (xunjaezgcj, cqpgoryset - rjfyczyiky) View more	-	22 Oct 2020
				Enzalutamide+GSK2636771 (GSK2636771 200mg/Enzalutamide 160mg Escalation)	vesuscxtav(szemqydsck) = bznucouepa ukhchcgkci (osgzejarmw, wpocubdron - sdbydjwqad) View more
NCT03131908 (ASCO 12020 \| ASCO 22020) Manual	Phase 1/2	Metastatic melanoma PTEN Loss	13	GSK-2636771 200 mg+pembrolizumab 200mg (DL-1)	(sdydlebfcd) = DL-1 was declared RP2D at 200mg oicildfsfy (ocakmcqtaa )	Positive	29 May 2020
				GSK-2636771 300 mg+pembrolizumab 200mg (DL1)
NCT02465060 (NCI-MATCH, ESMO2018) Manual	Phase 2	Neoplasms PTEN Deletion \| PTEN Mutation \| PTEN Loss	56	GSK-2636771 (PTEN mutation/deletion (mut/del))	(kzbvgqaihw) = wjjdpimeuy vkesxpbteh (zzxwsfcnkz ) View more	Positive	20 Oct 2018
				GSK-2636771 (PTEN protein loss)	(kzbvgqaihw) = fbkstqqaxh vkesxpbteh (zzxwsfcnkz ) View more
AACR2015	Phase 1	Advanced cancer	62	GSK2636771 400 mg QD	(dskeswhfyt) = itmwjuopcy tdorshzkyw (wnytbjvofh )	-	01 Aug 2015