A Multicenter, Open-Label, Randomized, Controlled Study to Assess the Antitumor Activity of LNS8801 With and Without Pembrolizumab in Patients With Treatment-Refractory, Unresectable Melanoma

The goal of this clinical trial is to understand if a new drug called LNS8801 can safely treat patients with melanoma. The primary question to be answered is what is the average length of time during which melanoma does not grow or spread after starting treatment with LNS8801? Researchers will compare LNS8801 taken alone or LNS8801 taken together with another drug called pembrolizumab to other therapies as decided by the treating doctor.
135 patients will be randomly (like flipping a coin) placed in 3 treatment groups.
In the first group (LNS8801 only) - Patients will take 125mg tablet of LNS8801 by mouth once per day every day for up to 2 years.
In the second group (LNS8801 + pembrolizumab) - Patients will take 125mg tablet of LNS8801 by mouth once per day plus 200 mg of pembrolizumab by IV infusion once every 3 weeks for up to 2 years.
In the third group, called Physician's Choice (PC), patients will receive chemotherapy (dacarbazine or temozolomide) or immunotherapy (pembrolizumab, nivolumab/relatlimab or nivolumab/ipilimumab) as determined by their treating physician.
How often the patient visits the clinic visits will depend on the treatment group. Besides returning to the clinic for treatment, the patient will undergo periodic safety assessments and other required study procedures such as imaging assessments.

开始日期2025-08-06

申办/合作机构

Linnaeus Therapeutics, Inc.

NCT04130516

/ Recruiting临床1/2期

A Multicenter Phase 1-2A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of LNS8801 in Patients With Advanced Cancer With and Without Pembrolizumab

This Phase 1/2, first-in-human, open-label, multicenter study follows a 3+3 ascending dose escalation design to determine the MTD/RP2D and to characterize the safety, tolerability, PK, and antitumor effects of LNS8801 alone and in combination with pembrolizumab. The study will include a dose escalation phase, a dose expansion phase, and phase 2A cohorts. Up to 200 patients will be accrued for this study. Up to 15 study sites in the United States will participate in the study.

开始日期2019-10-21

申办/合作机构

Linnaeus Therapeutics, Inc.

[+1]

100 项与 LNS-8801 相关的临床结果

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100 项与 LNS-8801 相关的转化医学

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100 项与 LNS-8801 相关的专利（医药）

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项与 LNS-8801 相关的文献（医药）

2025-07-08·Blood Advances

LNS-8801 as a therapeutic agent for aggressive lymphomas: ROS-induced cytotoxicity and synergy with existing therapies

Article

作者: Jin, Ling ; Lenz, Georg ; Li, Yang ; Schwammbach, Daniela ; Kosnopfel, Corinna ; Hailfinger, Stephan ; Grau, Michael

2025-04-01·Cancer research communications

LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

Article

作者: Natale, Christopher A. ; Aguirre-Portolés, Cristina ; Olayide, Israel ; Arnatt, Christopher K. ; Zhuang, Richard ; Ridky, Todd W. ; Garyantes, Tina K. ; Luke, Wayne ; Seykora, John T. ; Mercado, Sophia

Abstract:

Estrogen effects in tissue are mediated in part through activation of the surface estrogen receptor G protein–coupled estrogen receptor (GPER), a broadly expressed G protein–coupled receptor that affects a wide range of normal and pathologic processes, including metabolism, vascular health, inflammation, and cancer. A commonly used synthetic and specific GPER agonist, named G-1, antagonizes tumors by promoting cellular differentiation and enhancing tumor immunogenicity. G-1 is a racemic compound, and since its discovery, the question of whether both enantiomers display agonist activity or the agonist activity resides primarily in a single enantiomer has never been fully resolved. Herein, we disclose the isolation of the pure enantiomers of G-1 and determine that the desirable activity resides exclusively in one enantiomer, named LNS8801, whose configuration we have unambiguously determined by single-crystal X-ray structure analysis. Using preclinical models, we show that LNS8801 suppresses cancer in a GPER-dependent manner and that LNS8801 is efficacious when administered orally. Furthermore, we show that GPER is widely, but not ubiquitously, expressed in both normal and malignant human tissues. In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response.

Significance::

GPER is broadly expressed in human tissues and has tumor-suppressive activity. No FDA-approved agents selectively target GPER. LNS8801 is a synthetic, orally bioavailable, enantiomerically pure, GPER agonist with potent anticancer activity in vivo. LNS8801 response is attenuated by a common germline coding variant present in roughly half of humans.

2025-01-01·Pigment Cell & Melanoma Research

An In Vivo Study of LNS8801, a GPER Agonist, in a Spontaneous Melanoma‐Prone Mouse Model, TGS

Article

作者: Ridky, Todd ; Sauer, John ; Marinaro, Christina ; Chen, Suzie ; Natale, Christopher A.

ABSTRACT:

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G‐protein‐coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic exposure to sunlight. Over the course of the 32‐week experiment, visible images were taken by the small animal imaging IVIS system to track tumor progression, and blood and tissue samples were collected for molecular analyses. Results showed that sex‐biased effects were observed in the efficacy of LNS8801 and that LNS8801 shows a UV‐protective influence in both male and female TGS mice.

项与 LNS-8801 相关的新闻（医药）

2026-02-24

·BioSpace

Linnaeus Therapeutics Awarded Up to $22 Million from ARPA-H to Advance LNS8801 for Healthspan Preservation

ARPA-H PROSPR program to support accelerated development of LNS8801 to promote healthy aging HADDONFIELD, N.J., Feb. 24, 2026 (GLOBE NEWSWIRE) -- Linnaeus Therapeutics, Inc., a privately held company focused on the development and commercialization of small molecule therapeutics for diseases of aging, today announced it has been awarded a contract of up to $22 million from the Advanced Research Projects Agency for Health (ARPA-H). As part of the PROactive Solutions for Prolonging Resilience (PROSPR) program, Linnaeus will advance its lead drug-candidate, LNS8801, for the preservation of healthspan. This award will support a multiphase translational PROSPR research program designed to accelerate the development and evaluation of interventions that maintain physical and cognitive function and delay age-associated functional decline. The program will assess whether activation of the G protein-coupled estrogen receptor (GPER) with LNS8801 can preserve Intrinsic Capacity, defined as the integrated physical and cognitive abilities that underpin independence and resilience later in life. “Real-world data suggesting that women experience more favorable outcomes compared to men across multiple diseases of aging inspires our work at Linnaeus,” said Christopher Natale, PhD, Co-Founder and Chief Scientific Officer of Linnaeus Therapeutics and Principal Investigator on the award. “The PROSPR program will support studies that directly assess whether LNS8801 can preserve Intrinsic Capacity and improve healthspan.” LNS8801 is a first-in-class, only-in-class, oral, selective agonist of GPER with clinical evidence of biological activity across multiple physiological systems implicated in age-related functional decline and cancer. Under the PROSPR program, Linnaeus will conduct preclinical aging studies followed by a randomized clinical study in healthy older adults. These efforts will incorporate functional assessments, physiological and molecular biomarkers, and emerging measures of biological aging to enable efficient evaluation of healthspan-related outcomes. The program builds on prior clinical experience with LNS8801 in oncology, where more than 100 patients have been treated in a phase 1/2 study. In this study, LNS8801 demonstrated an exceptional safety and tolerability profile. Clinical data strongly suggest improved survival in patients with cancer, as well as clinically meaningful improvements in cardiometabolic measures, including LDL cholesterol, systolic blood pressure, Hb1AC, and weight loss. These data support further investigation of LNS8801 in multiple diseases of aging. “LNS8801 has a mechanism of action expected to provide benefits in multiple organ systems,” said Patrick Mooney, MD, Chief Executive Officer of Linnaeus Therapeutics. “ARPA-H’s evaluation of our data and subsequent award validates the promise of LNS8801 to potentially prevent diseases of aging and will enable a rigorous program to translate that promise into clinically meaningful improvements in healthspan-predictive outcomes.” “Since cardiometabolic health naturally declines with age, the preliminary data suggesting LNS8801 improves these in humans is compelling,” says Andrew Brack, ARPA-H Program Manager and creator of the PROSPR program. “That's why we’re excited to see whether this treatment will improve Intrinsic Capacity and healthspan.” This ARPA-H–supported work could establish a new preventive approach to medicine, preserving function and independence, rather than treating age-related diseases after decline has occurred. There are significant potential benefits for public health and healthcare sustainability. About LNS8801 LNS8801 is an orally bioavailable, highly selective agonist of the G protein-coupled estrogen receptor (GPER). In preclinical studies, GPER activation by LNS8801 has demonstrated activity across multiple biological pathways relevant to cancer, cardiometabolic health, inflammation, neurodegeneration, and tissue resilience. In ongoing clinical studies in patients with advanced cancers, LNS8801 monotherapy has been safe and well tolerated, with no dose-limiting toxicities observed. Clinical data have demonstrated target engagement and evidence of clinical activity, and a predictive biomarker associated with response has been identified. These findings, together with emerging cardiometabolic observations in patients treated with LNS8801, support continued evaluation of LNS8801 beyond oncology. About Linnaeus Therapeutics Linnaeus Therapeutics, Inc. is a privately held, clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel small-molecule therapeutics targeting G protein-coupled receptors. The company was founded based on discoveries originating at the University of Pennsylvania and launched in partnership with the UPstart incubator at the University of Pennsylvania’s Penn Center for Innovation (PCI). Linnaeus is supported by Kairos Ventures, Penn Medicine Co-Investment Fund at the University of Pennsylvania, and GenHenn Capital. Linnaeus is advancing LNS8801 across oncology and emerging healthspan-related indications through an integrated translational and clinical development strategy. Media Contact: Sarah Hall 6 Degrees (215) 313-5638 shall@6degreespr.com

临床结果

2025-03-26

·PRNewswire

Linnaeus Therapeutics Awarded Its Fourth Competitive SBIR Award by the National Cancer Institute Bringing Total SBIR Funding to $8.3 Million

$2,000,000 Direct-to-Phase 2 Award Funds Study of LNS8801 in the Treatment of Melanoma HADDONFIELD, N.J., March 26, 2025 /PRNewswire/ -- Linnaeus Therapeutics, Inc. ("Linnaeus"), a privately held biopharmaceutical company focused on the development and commercialization of novel small molecule oncology therapeutics, today announced it has been awarded its fourth competitive Small Business Innovation Research ("SBIR") Award by the National Cancer Institute ("NCI") of the National Institutes of Health ("NIH"). This $2,000,000 SBIR award was granted to the company after yet another highly competitive peer-review process. The award will help fund the clinical development of its lead compound, LNS8801, which targets a G protein-coupled receptor (GPER), for the treatment of metastatic cutaneous melanoma as a monotherapy in patients who cannot tolerate immunotherapy. "This award marks the fourth time that Linnaeus has received a competitive award from NCI for LNS8801 development and brings the total non-dilutive contribution by NCI to LNS8801 development to $8.3 million. NCI's continued support provides a strong peer-reviewed validation of the core science that is the basis of LNS8801, its target GPER, and the clinical data seen in LNS8801-treated patients with cancer," said Patrick Mooney, MD, Chief Executive Officer of Linnaeus. "This award will allow us to further advance LNS8801 as a potentially safe and effective oral therapeutic for the treatment of melanoma and will augment the data seen from our ongoing clinical studies of LNS8801. We thank the NCI and NIH for their ongoing support of LNS8801 to help patients with cancer." Linnaeus anticipates initiating a randomized controlled clinical trial in unresectable, treatment refractory cutaneous melanoma in Q2 of this year. This study will randomize 135 biomarker-positive patients to receive LNS8801 monotherapy, LNS8801 and pembrolizumab, or physician's choice therapy. The study will assess progression-free survival and overall survival between the groups. About LNS8801 LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. In the ongoing clinical study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and durable clinical benefit in patients with advanced cancers, and a predictive biomarker has been identified. About Linnaeus Linnaeus Therapeutics, Inc. is a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small molecule oncology therapeutics that target G protein-coupled receptors. The company was formed and launched in partnership with the UPstart incubator at the University of Pennsylvania's Penn Center for Innovation (PCI). SOURCE Linnaeus Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

免疫疗法临床2期ASCO会议

2024-09-16

·PRNewswire

Linnaeus Therapeutics Announces Presentation of Positive Clinical Data of LNS8801 in Metastatic Melanoma at 2024 ESMO Annual Meeting

HADDONFIELD, N.J., Sept. 16, 2024 /PRNewswire/ -- Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, today announced the presentation of clinical data at the 2024 ESMO Annual Meeting from its dose-expansion cohort of LNS8801 as a monotherapy in patients with metastatic cutaneous melanoma who could not tolerate immunotherapy due to prior immune-related adverse events. The poster is entitled "Efficacy of LNS8801 in melanoma patients with prior immune-related adverse events from immune-checkpoint inhibitors" (Abstract 1137P). LNS8801 given alone was tolerable without unanticipated toxicities and demonstrated encouraging antitumor activity in patients with metastatic cutaneous melanoma who had prior severe immune-related adverse events on immune checkpoint inhibitor therapies. LNS8801 monotherapy treatment resulted in a disease control rate of 100% in biomarker-positive patients, with a preliminary progression-free survival of over 6 months. This includes a patient that has been on treatment for over 4.5 years with resolution of all soft-tissue lesions and no evidence of active disease in the residual bone-associated target lesion or elsewhere. "We are extremely pleased to showcase these data at ESMO," commented Patrick Mooney, MD, CEO of Linnaeus. "The data from this study demonstrate that LNS8801 is extremely safe and well tolerated and shows very promising signs of efficacy. Given that patients with prior irAEs are often prevented from receiving further immunotherapy, these patients represent a large unmet need. We look forward to generating more data in this patient population and in unresectable treatment refractory melanoma." Linnaeus anticipates initiating a randomized controlled clinical trial in unresectable, treatment-refractory cutaneous melanoma in Q4 of this year. This study will randomize 135 biomarker-positive patients to receive LNS8801 monotherapy; LNS8801 and pembrolizumab; or physician's choice therapy. The study will assess median progression-free survival and overall survival among the groups. About LNS8801 LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. In the ongoing clinical study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancers, and a predictive biomarker has been identified. About Metastatic Cutaneous Melanoma Although there has been progress in the treatment of metastatic cutaneous melanoma, most patients will progress on standard of care therapies and need further treatment. According to the American Cancer Society, almost 8,000 patients die each year in the United States, highlighting the need for safe and effective therapies in the treatment-refractory setting. About Linnaeus Linnaeus Therapeutics, Inc. is a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small molecule oncology therapeutics that target G protein-coupled receptors. The company was formed and launched in partnership with the UPstart incubator at the University of Pennsylvania's Penn Center for Innovation (PCI). SOURCE Linnaeus Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果免疫疗法ASCO会议

100 项与 LNS-8801 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
皮肤黑色素瘤	临床3期	美国	Linnaeus Therapeutics, Inc.	2025-08-06
不可切除的黑色素瘤	临床3期	美国	Linnaeus Therapeutics, Inc.	2025-08-06
晚期癌症	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
晚期恶性实体瘤	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
结直肠癌	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
淋巴瘤	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
转移性非小细胞肺癌	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
葡萄膜黑色素瘤	临床2期	美国	Linnaeus Therapeutics, Inc.	2019-10-21
胰腺导管腺癌	临床前	美国	Linnaeus Therapeutics, Inc.	2020-01-01
胰腺导管腺癌	临床前	美国	University of Pennsylvania	2020-01-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04130516 (LNS8801, ESMO2024)	临床1期	黑色素瘤 germline GPER	9	LNS8801 125 mg	遞壓廠觸夢積淵鑰廠壓(衊窪醖獵積繭醖願觸遞) = G3 and G1 壓製憲艱願積顧範鹹窪 (鏇簾築壓襯鏇築廠鑰築 ) 更多	积极	2024-09-14
NCT04130516 (SITC2023)	临床1/2期	难治性黑色素瘤 consensus germline GPER	10	LNS8801 + pembrolizumab	顧鏇窪餘糧製顧製衊獵(壓網築窪廠蓋鑰簾鹽鹽) = 積製膚膚築齋鹽淵願遞範醖夢齋築齋鑰鏇餘窪 (顧膚遞艱廠構範鏇膚艱 ) 更多	积极	2023-11-02
NCT04130516 (ESMO2023)	临床1/2期	难治性黑色素瘤	-	LNS8801 (125 mg, QD, PO) + Pembrolizumab (200 mg, Q3W, IV)	醖鹹窪夢簾鬱鏇夢遞製(襯壓鑰觸製窪蓋積膚構) = 餘製築窪願構淵膚鑰壓夢選廠夢獵積顧衊憲遞 (鏇觸築餘積遞壓遞憲製 ) 更多	-	2023-10-22
NCT04130516 (ASCO2023) 人工标引	临床1/2期	葡萄膜黑色素瘤	15	LNS8801 125 mg	鑰網糧選鬱積繭積窪鹹(製餘衊夢憲遞製蓋膚簾) = 4 of 8 monotherapy patients had AEs potentially related to study drug (all grade 1), with no AEs occurring in more than one patient. 6 of 7 combination patients had AEs potentially related to study drugs (grades 1-2), with fatigue occurring in more than one patient. 衊遞構鹽簾鑰襯餘鏇鏇 (憲遞淵願鹽觸鏇積範淵 )	积极	2023-05-31
NCT04130516 (ASCO2023) 人工标引	临床1/2期	葡萄膜黑色素瘤	15	LNS8801 125 mg+pembrolizumab 200 mg		积极	2023-05-31
NCT04130516 (Corporate Publications) 人工标引	临床1/2期	肿瘤	13	LNS8801+Pembrolizumab	鹽鏇獵膚構獵糧遞艱顧(窪積齋窪鑰遞淵遞鬱蓋) = LNS8801 was identified as 125 mg daily as a monotherapy and in combination with pembrolizumab (200 mg every 3 weeks) 選糧構蓋構築選網糧鬱 (選獵艱鹹壓鹽膚遞鹽製 )	积极	2022-06-06
NCT04130516 (ASCO2022) 人工标引	临床1期	实体瘤	13	LNS8801 125 mg+pembrolizumab 200 mg	鬱夢憲膚齋餘襯窪艱鑰(艱膚鏇製廠範壓糧壓廠) = 艱鏇獵鹽簾壓衊餘範廠餘獵膚繭構夢夢憲積築 (選窪積願築鬱選鬱構鹽 ) 更多	积极	2022-06-02
NCT04130516 (ASCO 12021 \| ASCO 22021) 人工标引	临床1期	恶性实体肿瘤	33	LNS8801	夢襯壓壓糧獵觸壓顧襯(鏇構鏇餘獵壓鬱網醖蓋) = 鑰築膚膚夢醖醖遞膚鹹製壓齋選獵遞顧窪遞衊 (壓膚選繭壓鹹網獵齋蓋 ) 更多	积极	2021-05-20
NCT04130516 (ASCO 12021 \| ASCO 22021) 人工标引	临床1期	恶性实体肿瘤	33	LNS8801+pembrolizumab	夢襯壓壓糧獵觸壓顧襯(鏇構鏇餘獵壓鬱網醖蓋) = 觸淵鬱窪遞壓餘膚壓蓋製壓齋選獵遞顧窪遞衊 (壓膚選繭壓鹹網獵齋蓋 ) 更多	积极	2021-05-20