Delving into the Latest Updates on GTx-758 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Capesaris, GTX 758, GTx-758

Target

ERα

Action

agonists

Mechanism

ERα agonists(Estrogen receptor alpha agonists)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Advanced Prostate Carcinoma

Inactive Indication

Bone metastasesCastration-Resistant Prostatic CancerMetastatic castration-resistant prostate cancer

Originator Organization

GTx, Inc.

Active Organization

Urologic Consultants

San Bernardino Medical Group, Inc.

University of Washington

+ [6]

Inactive Organization

GTx, Inc.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Protocol G200712 is a Phase II, exploratory study to assess the effects of GTx-758 on serum prostate specific antigen (PSA) response ans serum PSA progression in men with Metastatic Castration Resistant Prostate Cancer (mCRPC) on Androgen Deprivation Therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists, or orchidectomy. This study will also assess the venous thromboembolism (VTE) risk of lower doses of GTx-758.

Start Date14 Aug 2012

Sponsor / Collaborator

GTx, Inc.

NCT01420861

/ TerminatedPhase 2

Open Label Study of the Effect of GTx-758 on Serum PSA and Free Testosterone Levels in Men With Castration Resistant Prostate Cancer and Maintained on Androgen Deprivation Therapy

The purpose of this study is to assess the effect of GTx-758 on Serum Prostate-specific antigen (PSA) levels in men with castrate resistant prostate cancer who are maintained on androgen deprivation therapy (Serum PSA response and Serum PSA progression)

Start Date01 Sep 2011

Sponsor / Collaborator

GTx, Inc.

NCT01393119

/ TerminatedPhase 2

Phase II, Open-label, Loading and Maintenance Dose Finding Study of GTx-758 in Men With Prostate Cancer

The purpose of this study is to determine the appropriate loading and maintenance dose of GTx-758 to reach and maintain castration for the duration of the study.

Start Date01 Aug 2011

Sponsor / Collaborator

GTx, Inc.

100 Clinical Results associated with GTx-758

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100 Translational Medicine associated with GTx-758

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100 Patents (Medical) associated with GTx-758

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4

Literatures (Medical) associated with GTx-758

01 Dec 2020·Clinical genitourinary cancerQ3 · MEDICINE

Phase 2 Trial of GTx-758, an Estrogen Receptor Alpha Agonist, in Men With Castration-Resistant Prostate Cancer

Q3 · MEDICINE

Article

Author: Getzenberg, Robert H ; Taylor, Ryan ; Hancock, Michael L ; Flaig, Thomas ; Yu, Evan Y ; Hardigan, Patrick C ; Aronson, William ; Tutrone, Ronald ; Belkoff, Laurence

INTRODUCTION:

Novel estrogen therapy has the potential to be efficacious, with a favorable adverse event profile, in castration-resistant prostate cancer (CRPC). We performed a phase 2 trial to assess the ability of GTx-758, an oral selective estrogen receptor alpha agonist, to result in a ≥ 50% PSA decline by day 90, modulate free testosterone and sex hormone-binding globulin (SHBG) levels, and affect estrogen deficiency adverse events.

PATIENTS AND METHODS:

CRPC patients received GTx-758 in two dose cohorts, 125 and 250 mg/d. The primary endpoint was the proportion of subjects who experienced a ≥ 50% PSA decline by day 90. Secondary endpoints included changes in testosterone, SHBG, bone turnover markers, and hot flashes, as well as safety.

RESULTS:

Four (10.5%) of 38 (95% CI, 2.9, 24.8; P = .120) and 10 (25.6%) of 39 patients (95% CI, 13.0, 42.1; P < .001) in the GTx-758 125 and 250 mg/d cohorts, respectively, experienced ≥ 50% PSA decline. SHBG was increased, providing a mechanism for notable decreases in free testosterone. In the 250 mg/d cohort, 9 men presented with moderate to severe hot flashes, and after 12 weeks, 4 (44%) of 9 reported either mild or no hot flashes (P = .001). The rate of venous thromboembolic events was 0% and 5.1% in the 125 and 250 mg/d arms, respectively.

CONCLUSION:

GTx-758 has clinical activity for CRPC in a dose-dependent fashion. GTx-758 resulted in a reduction in hot flashes. On the basis of these findings, further clinical investigation of novel estrogen therapies is warranted.

01 Feb 2015·European urologyQ1 · MEDICINE

Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer

Q1 · MEDICINE

Article

Author: Coss, Christopher C ; Gaylis, Franklin ; Yu, Evan Y ; Getzenberg, Robert H ; Keane, Thomas ; Chu, Franklin ; Gambla, Michael ; Dalton, James T ; Hancock, Michael L ; Belkoff, Laurence ; Given, Robert ; Gittelman, Marc M ; Bailen, James ; Bass, Joel ; Smith, Jordan ; Steiner, Mitchell S ; Tutrone, Ronald

BACKGROUND:

A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course.

OBJECTIVE:

To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy.

DESIGN, SETTING, AND PARTICIPANTS:

Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot.

INTERVENTION:

GTx-758 and leuprolide.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels.

RESULTS AND LIMITATIONS:

Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%).

CONCLUSIONS:

Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs.

PATIENT SUMMARY:

This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events.

TRIAL REGISTRATION:

Clinicaltrials.gov identifier NCT01615120.

01 Aug 2014·Nature reviews. UrologyQ1 · MEDICINE

GTx-758 reduces testosterone

Q1 · MEDICINE

Article

Author: Fenner, Annette

100 Deals associated with GTx-758

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External Link

KEGG	Wiki	ATC	Drug Bank
-	GTx-758	-	DB14969

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bone metastases	Phase 2	Hungary	GTx, Inc.	25 Jan 2013
Metastatic Prostate Carcinoma	Phase 2	Hungary	GTx, Inc.	25 Jan 2013
Metastatic castration-resistant prostate cancer	Phase 2	United States	GTx, Inc.	14 Aug 2012
Castration-Resistant Prostatic Cancer	Phase 2	United States	GTx, Inc.	01 Sep 2011
Advanced Prostate Carcinoma	Phase 2	United States	GTx, Inc.	01 Jun 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01393119 (CTgov)	Phase 2	Prostatic Cancer	77	GTx-758 (1000mg GTx-758 BID)	zpabgkskhq = rqbefayllh tudfwgpdbg (gkwgbsirad, wyhgbqhcvn - exzrdjsaqt) View more	-	22 Apr 2024
				GTx-758 (1500 mg GTx-758 BID)	zpabgkskhq = buzftnbbxu tudfwgpdbg (gkwgbsirad, gxtelmhsij - onajtjtpph) View more
NCT01420861 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	18	GTx-758	jxlefmqokh = xiffecfmaw rotvqnfrlg (fhkodzuizg, qifofkrofo - qpzluhdrkc) View more	-	06 Oct 2023
NCT01326312 (G200705 \| GTx758, CTgov)	Phase 2	Prostatic Cancer \| Advanced Prostate Carcinoma	159	GTx-758 2000mg (GTx- 758 1000mg)	lmdawqwlew = veowmlvkan yxltgvxdja (wyeedauqrv, xfcazqpuvo - inncckuela) View more	-	22 Jun 2023
				GTx-758 1000mg (GTx-758 2000mg)	lmdawqwlew = uuvyccibfg yxltgvxdja (wyeedauqrv, qmfqzcrkbw - oleeddzwaj) View more
NCT01615120 (G200712, CTgov)	Phase 2	Metastatic castration-resistant prostate cancer	77	GTx-758 (GTx-758 125mg)	bkovnsmzxq = pgptjbixxf exzvqblkpy (cixllyksot, sifllfdinp - jlootfpokq) View more	-	16 Feb 2021
				GTx-758 250 mg (GTx-758 250 mg)	bkovnsmzxq = fmjicsuwbm exzvqblkpy (cixllyksot, yccwczuzqq - cdceiakqxs) View more
NCT01615120 (Pubmed \| Clin Genitourin Cancer) Manual	Phase 2	Castration-Resistant Prostatic Cancer	77	GTx-758 (125mg/d cohorts)	rjdbvuemoq(yuicabtbsc) = myyuilelrw afnppwrciw (bscfxpobwh, 2.9 - 24.8)	Positive	01 Dec 2020
				GTx-758 (250mg/d cohorts)	rjdbvuemoq(yuicabtbsc) = zjmvcifozc afnppwrciw (bscfxpobwh, 13.0 - 42.1)
NCT01615120 (G200712, AUA2016)	Phase 2	Castration-Resistant Prostatic Cancer SHBG \| testosterone	39	250 mg GTx-758	hkahdpvpqo(aofxolkuvq) = two reported possibly drug related SAEs (VTE and MI) ymyizhjpdw (zmcpvohxwm ) View more	-	01 Apr 2016
NCT01615120 (G200712, ASCO_GU2016)	Phase 2	Castration-Resistant Prostatic Cancer	39	GTx-758 250 mg	fawgnsbsyc(bvbjuduluo) = rqmzywlsei ezuqlpmfqy (vucgsqsfxs )	Positive	10 Jan 2016
NCT01615120 (G200712, ASCO2015)	Phase 2	Castration-Resistant Prostatic Cancer	33	GTx-758 250 mg	lenjvvrhah(swcuckxeog) = one reported possibly drug related SAE (VTE) aahakusorx (wlgzmpqrlj )	-	20 May 2015
NCT01326312 (G200705, ASCO2013)	Phase 2	Advanced Prostate Carcinoma	159	GTx-758 1000 mg	irswysimqr(vfzxqoszoa) = kpuwaxfkiw wdmsbmwapg (dlydtbfflz )	-	20 May 2013
				GTx-758 2000 mg	irswysimqr(vfzxqoszoa) = vxicxjsael wdmsbmwapg (dlydtbfflz )
NCT01326312 (ASCO_GU2013)	Phase 2	Advanced Prostate Carcinoma	159	GTx-758 1000 mg	qtwrtgmbzw(ygnupvnfpw) = cnltbzngmp pzbyzjdsrr (cqlopjuegt ) View more	-	20 Feb 2013
				GTx-758 2000 mg	qtwrtgmbzw(ygnupvnfpw) = jkqtwizbqr pzbyzjdsrr (cqlopjuegt ) View more