(ATL-101(Cornell University)) - 药物靶点：PSMA_在研适应症：前列腺癌_专利_临床

概要

基本信息

药物类型

抗体偶联核素、治疗用放射药物

别名

Anti-PSMA monoclonal antibody J591、Anti-PSMA-monoclonal-antibody-J-591-Lu-177、Lutetiu

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靶点

PSMA

作用机制

PSMA抑制剂(前列腺癌特异性膜抗原抑制剂)、电离辐射发射源

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

Weill Medical College of Cornell UniversityBZL Biologics LLC

Millennium Pharmaceuticals, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

序列信息

Sequence Code 213724VL

Sequence Code 1117836298VH

关联

7

项与 ATL-101(Cornell University) 相关的临床试验

NCT02693860 / Completed临床1期IIT

A Pilot Study of Neoadjuvant Monoclonal Antibody Humanised (hu) J591 for the Treatment of High and/or Intermediate-Risk Prostate Cancer

10 patients will be enrolled in the initial cohort and will receive two infusions of unlabeled huJ591 on days 1 and 14. 89Zr-J591 will be administered on day 21 (+ 1 day) and a positron emission tomography-computed tomography (PET/CT) will be performed week later on day 28 + 1 (visit 4). Approximately 2 to 3 weeks after the 2nd dose of J591, the patient will undergo radical prostatectomy with or without lymph node dissection (day 31 + 4 days). The final visit for the study will include a postoperative visit two weeks following surgery.

开始日期2016-02-04

申办/合作机构

Weill Medical College of Cornell University

NCT02552394 / Completed临床1期IIT

Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Patients With Advanced Prostate Cancer and Unfavorable Circulating Tumor Cell Counts

This clinical trial is for men with advanced prostate cancer that may have spread to other parts of the body.
Currently, once prostate cancer cells have spread from the prostate to other organs it is not treatable by surgery. The purpose of this study is to treat patients with an experimental antibody (i.e. that has not been FDA approved) called J591 that attaches itself to a special protein on cancer cells called PSMA to try to eliminate these cancer cells (called circulating tumor cells) from the circulation.
In the initial phase of the study, 6 participants will receive the experimental J591 treatment. Routine blood tests, research blood tests, physical exam will be performed at each visit. Participants will also be asked to complete a questionnaire about how they are feeling. Participants will have a radiographic scan every 3 months to check the status of their disease.
Participants who tolerate the treatment well may be re-treated at the same level every 3 months, and may continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

开始日期2015-07-01

申办/合作机构

Weill Medical College of Cornell University

NCT00967577 / Completed临床1期IIT

177Lu Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Nonprostate Metastatic Solid Tumors: A Pilot Study

The purpose of this study is to evaluate changes in tumor blood flow and disease response to the investigation agent, 177Lu-J591.

开始日期2009-07-01

申办/合作机构

Weill Medical College of Cornell University

100 项与 ATL-101(Cornell University) 相关的临床结果

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100 项与 ATL-101(Cornell University) 相关的转化医学

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100 项与 ATL-101(Cornell University) 相关的专利（医药）

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62

项与 ATL-101(Cornell University) 相关的文献（医药）

2024-01-29·Annual review of medicine

Prostate-Specific Membrane Antigen: Gateway to Management of Advanced Prostate Cancer.

Review

作者: Lena M Unterrainer ; Jeremie Calais ; Neil H Bander

Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization. However, it remains to be demonstrated how to integrate PSMA PET imaging for therapy response assessment and as an outcome endpoint measure in clinical trials. With the recent approval of ¹⁷⁷Lu-PSMA-617 by the US Food and Drug Administration for metastatic castration-resistant PC progressing after chemotherapy, the high value of PSMA-targeted therapy was confirmed. Compared to standard of care, PSMA-based radioligand therapy led to a better outcome and a higher quality of life. This review, focusing on the advanced PC setting, provides an overview of different approved and nonapproved PSMA-targeted imaging and therapeutic modalities and discusses the future of PSMA-targeted theranostics, also with an outlook on non-radiopharmaceutical-based PSMA-targeted therapies.

2023-11-03·Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of ²²⁵Ac-J591.

Article

作者: Scott T Tagawa ; Charlene Thomas ; A Oliver Sartor ; Michael Sun ; Judith Stangl-Kremser ; Mahelia Bissassar ; Shankar Vallabhajosula ; Sandra Huicochea Castellanos ; Jones T Nauseef ; Cora N Sternberg ; Ana Molina ; Karla Ballman ; David M Nanus ; Joseph Osborne ; Neil H Bander

PURPOSE:

Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface antigen overexpressed in PC, provides a validated target. This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for ²²⁵Ac-J591, anti-PSMA monoclonal antibody J591 radiolabeled with the alpha emitter actinium-225.

METHODS:

Following investigational new drug-enabling preclinical studies, we enrolled patients with progressive mCRPC that was refractory to or who refused standard treatment options (including androgen receptor pathway inhibitor and had received or been deemed ineligible for taxane chemotherapy). No selection for PSMA was performed. Patients received a single dose of ²²⁵Ac-J591 at one of seven dose-escalation levels followed by expansion at the highest dose. Primary end point of dose-escalation cohort was determination of dose-limiting toxicity (DLT) and RP2D.

RESULTS:

Radiochemistry and animal studies were favorable. Thirty-two patients received ²²⁵Ac-J591 in an accelerated dose-escalation design (22 in dose escalation, 10 in expansion). One patient (1 of 22; 4.5%) experienced DLT in cohort 6 (80 KBq/kg) but none in cohort 7; MTD was not reached, and RP2D was the highest dose level (93.3 KBq/kg). The majority of high-grade adverse events (AEs) were hematologic with an apparent relationship with administered radioactivity. Nonhematologic AEs were generally of low grade. Prostate-specific antigen (PSA) declines and circulating tumor cell (CTC) control were observed: 46.9% had at least 50% PSA decline at any time (34.4% confirmed PSA response), and protocol-defined CTC count response occurred in 13 of 22 (59.1%).

CONCLUSION:

To our knowledge, this is the first-in-human phase I dose-escalation trial of a single dose of ²²⁵Ac-J591 in 32 patients with pretreated progressive mCRPC demonstrated safety and preliminary efficacy signals. Further investigation is underway.

2023-07-09·The Prostate

Prognostic value of neutrophil-to-lymphocyte ratio in patients with metastatic castration-resistant prostate cancer receiving prostate-specific membrane antigen targeted radionuclide therapy.

Article

作者: Judith Stangl-Kremser ; Michael Sun ; Benedict Ho ; Joseph Thomas ; Jones T Nauseef ; Joseph R Osborne ; Ana Molina ; Cora N Sternberg ; David M Nanus ; Neil H Bander ; Scott Tagawa

BACKGROUND:

Neutrophil count:lymphocyte count ratio (NLR) may be a prognostic factor for men with advanced prostate cancer. We hypothesized that it is associated with prostate-specific antigen (PSA) response and survival in men treated with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT).

METHODS:

Data of 180 men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in sequential prospective radionuclide clinical trials from 2002 to 2021 (utilizing 177Lu-J591, 90Y-J591, 177Lu-PSMA-617, or 225Ac-J591) were retrospectively analyzed. We used a logistic regression to determine the association between NLR and ≥50% PSA decline (PSA50) and a Cox proportional hazards model to investigate the association between NLR and overall survival (OS).

RESULTS:

A total of 94 subjects (52.2%) received 177Lu-J591, 51 (28.3%) 177Lu-PSMA-617, 28 (15.6%) 225Ac-J591, and 7 (3.9%) 90Y-J591. The median NLR of 3.75 was used as cut-off (low vs. high NLR; n = 90, respectively). On univariate analysis, NLR was not associated with PSA50 (HR 1.08; 95% confidence interval [CI] 0.99-1.17, p = 0.067). However, it was associated with worse OS (hazard ratio [HR] 1.06, 95% CI 1.02-1.09, p = 0.002), also after controlling for circulating tumor cell count and cancer and leukemia group B risk group (HR 1.05; 95% CI 1.003-1.11, p = 0.036). Men with high NLR were at a higher hazard of death from all causes (HR 1.43, 95% CI 1.05-1.94, p = 0.024).

CONCLUSIONS:

NLR provides prognostic information in the setting of patients with mCRPC receiving treatment with PSMA-TRT.

100 项与 ATL-101(Cornell University) 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
前列腺癌	临床2期	-	Weill Medical College of Cornell University 更多

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00538668 (ASCO_GU2016)	临床1期	前列腺癌 prostate specific membrane antigen	48	<sup>177</sup>Lu-J591 40 mCi/m2 x2	(齋衊鬱艱築構襯鹹製膚) = 72.9% had grade 3/4 hematological toxicities; 19 (59.4%) with Gr 4 heme toxicity in RP2D cohorts, with 15 (16.9%) receiving at least 1 platelet transfusion, 6 receiving GCSF, and 0 with febrile neutropenia 糧糧構獵鏇築衊壓窪鑰 (獵獵築獵築憲網醖選鹹 ) 更多	积极	2016-01-10
PD16-11 (AUA2020)	N/A	PSMA阳性前列腺癌	-	177Lu-J591	(壓衊鏇餘鬱鬱艱選襯艱) = 遞網鬱網膚淵遞構淵遞鏇廠齋鑰遞繭憲鹽鬱衊 (鏇糧廠觸膚願鹽製襯繭 )	-	2020-04-01
				177Lu-PSMA-617	(壓衊鏇餘鬱鬱艱選襯艱) = 築觸築餘築廠繭憲壓鏇鏇廠齋鑰遞繭憲鹽鬱衊 (鏇糧廠觸膚願鹽製襯繭 )
NCT00195039 (ASCO_GU2013)	临床2期	去势抵抗性前列腺癌	47	<sup>177</sup>Lu-J591 at 65 mCi/m<sup>2</sup>	(憲鹽鏇襯膚鏇鏇鹽範網) = More PSA declines and longer OS were seen at 70 mCi/m² 鹹製鏇淵蓋齋齋襯衊網 (窪窪簾積網廠膚糧衊淵 )	-	2013-02-20
				<sup>177</sup>Lu-J591 at 70 mCi/m<sup>2</sup>
AUA2021	N/A	转移性去势抵抗性前列腺癌	-	177Lu-J591	鏇齋繭積夢顧願齋鏇製(憲衊願願壓窪淵艱糧繭) = 繭範窪鬱構艱願壓獵膚網範築鏇壓簾憲積鏇蓋 (顧簾鹽壓構觸膚構製鹹 ) 更多	-	2021-09-01
				177Lu-PSMA-617	(簾積憲鬱鑰製選遞遞願) = 蓋蓋糧積齋壓鑰築顧範鹹顧衊築鏇鑰願醖築願 (醖簾積構蓋鬱蓋簾淵製 )
AACR2012	临床1期	转移性去势抵抗性前列腺癌	28	Fractionated-dose 177Lutetium radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591	廠淵繭艱膚顧願構蓋觸(廠願網簾廠鹽淵壓獵積) = 淵選鏇網築鏇艱顧顧顧顧艱醖夢構選顧襯簾夢 (窪襯築積糧衊網醖觸鹹 ) 更多	-	2012-04-15
AUA2016	临床1/2期	转移性去势抵抗性前列腺癌	48	177Lu-J591	(願遞憲衊膚襯膚憲壓願) = 繭鑰獵構鹽夢顧鏇憲淵簾廠顧齋餘餘範選襯餘 (選觸鬱鬱鏇網鏇獵網艱 ) 更多	-	2016-04-01
NCT00195039 (ASCO_GU2015)	临床1/2期	PSMA阳性前列腺癌 prostate-specific membrane antigen (PSMA)	48	<sup>177</sup>Lu-J591	(遞壓憲窪膚憲簾膚壓繭) = 鬱選獵窪膚網夢鹽繭構築獵選網齋獵簾壓鹽鑰 (鹽憲鏇構遞淵艱網獵鬱 )	-	2015-03-01
ASCO_GU2011	临床1期	PSMA阳性肿瘤 PSMA	132	<sup>177</sup>Lu-J591	(鹽構窪鏇夢築鬱網蓋獵) = 製壓簾憲憲簾衊淵遞顧鏇膚襯選範淵鏇遞顧襯 (築齋製選淵鬱簾範繭遞 ) 更多	-	2011-03-01
				<sup>90</sup>Y-J591	(鹹簾齋艱遞淵鏇醖糧構) = 鹽鏇廠鹽構繭鹹遞艱網鬱積遞鏇選範鏇糧繭餘 (繭獵製鬱獵糧獵齋膚憲 )
NCT00538668 (ASCO2016)	临床1期	转移性去势抵抗性前列腺癌	49	<sup>177</sup>Lu-J591 40 mCi/m<sup>2</sup> x2	艱窪範憲積顧範遞鹽積(窪範鏇廠壓遞膚選醖獵) = 5 (10.2%) had transient Gr 1/2 AST/ALT 醖網觸簾膚憲糧製願遞 (遞餘鏇構窪願構艱衊鏇 ) 更多	-	2016-05-20
				<sup>177</sup>Lu-J591 45 mCi/m<sup>2</sup> x2
NCT00916123 (Pubmed) 人工标引	临床1期	转移性去势抵抗性前列腺癌	15	docetaxe+177 Lu-J591	(觸憲廠顧製鑰壓築願窪) = 2.96 GBq/m2 鑰夢醖淵鹹鬱夢蓋齋獵 (鑰壓鬱齋壓鹹衊築蓋範 ) 更多	积极	2020-11-01