Evaluating the safety and logistics of Tarloxotinib combined with Stereotactic Body RadiationTherapy (SBRT) in a window of opportunity trial of advanced Human Papilloma Virus (HPV) negative head & neck cancer.

开始日期2023-10-12

申办/合作机构-

NCT05313009

/ Terminated临床1/2期

A Phase Ib / II Trial of Tarloxotinib and Sotorasib in Patients With KRAS G12C Mutations

This is a Phase IB dose expansion trial with safety lead-in evaluating the safety, clinical activity/efficacy of the combination of tarloxotinib and sotorasib in patients with KRAS G12C mutation who have progressed on any small molecule targeting KRAS G12C mutant Non-Small Cell lung cancer.

开始日期2022-03-07

申办/合作机构

The Medical University of South Carolina

[+1]

NCT03805841

/ Terminated临床2期

Phase 2 Study - Evaluate the Clinical Activity of Tarloxotinib in Patients With Non-Small Cell Lung Cancer That Harbors an EGFR Exon 20 Insertion or HER2-Activating Mutation and Other Advanced Solid Tumors With NRG1/ERBB Family Gene Fusions

Open-label, Phase 2, single treatment arm, 3 cohorts

开始日期2019-03-13

申办/合作机构

Rain Oncology, Inc.

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100 项与 Tarloxotinib Bromide 相关的专利（医药）

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项与 Tarloxotinib Bromide 相关的文献（医药）

2025-05-01·ANTIVIRAL RESEARCH

Assessment of repurposed compounds against coronaviruses highlights the antiviral broad-spectrum activity of host-targeting iminosugars and confirms the activity of potent directly acting antivirals

Article

作者: Hill, Michelle L ; Gileadi, Carina ; Kiappes, J L ; Brun, Juliane ; Witt, Karolina D ; Dwek, Raymond A ; von Delft, Annette ; Arman, Benediktus Yohan ; Rangel, Victor ; Makower, Laetitia L ; Zitzmann, Nicole ; Alonzi, Dominic S

The COVID-19 pandemic highlights the need for novel antiviral drug discovery approaches that could dramatically shorten timelines from compound discovery to clinical development. At the beginning of the pandemic, repurposing approaches were at the forefront of early research efforts to screen for antiviral activity against SARS-CoV-2 in over 2500 compounds. Here, we report cellular screening results of 100 FDA-approved and experimental compounds against SARS-CoV-2 in the human Calu-3 cell line. We observed 13 compounds showing antiviral activity against SARS-CoV-2, including seven FDA-approved compounds (remdesivir, boceprevir, amiloride, nafamostat, cisplatin, silmitasertib, and miglustat), and six compounds in pre-clinical and clinical development (tarloxotinib, lucerastat (NB-DGJ), MON-DNJ, NAP-DNJ, NN-DGJ and NN-DNJ). Further, we observed that our screening hits include several host-targeting antivirals, namely iminosugars, that are largely non-toxic and offer a large therapeutic window. The most-developed iminosugar MON-DNJ (UV-4B), which has been evaluated in a Phase 1 clinical trial, shows antiviral activity against SARS-CoV-2 wild type as well as alpha, beta, gamma, delta, and Omicron variants. Its activity also extended to another betacoronavirus HCoV OC43, but not alphacoronavirus HCoV 229E. Our cellular screening results add to the body of knowledge on antivirals against coronaviruses and confirm the antiviral efficacy of iminosugars in cellular assays using the human lung-cell line Calu-3.

2024-10-01·EUROPEAN JOURNAL OF CANCER

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer

Article

作者: Santini, Fernando C ; Pike, Luke R G ; Scher, Howard I ; Chandarlapaty, Sarat ; Gupta, Avantika ; Isbell, James M ; Liu, Si-Yang ; Jones, David R ; Schoenfeld, Adam ; Gagne, Eric ; Rudin, Charles M ; Lee, Nancy Y ; Gomez, Daniel R ; Arfe, Andrea ; Chang, Jason ; Riaz, Nadeem ; Sui, Jane ; Li, Bob T ; Eichholz, Jordan ; Razavi, Pedram ; Erazo, Tatiana ; Travis, William ; Kris, Mark G ; Johnson, Kaylie ; Drilon, Alexander ; Jee, Justin ; Yang, Soo-Ryum ; Martinez, Andres ; Baehner, Frederick ; Daly, Bobby ; Garg, Kavita ; Guo, Jiannan ; Arcila, Maria E

INTRODUCTION:

No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment.

METHODS:

We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS).

RESULTS:

Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019).

CONCLUSION:

Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

2024-03-01·Archives of toxicology

TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer

Article

作者: Ding, Yongbin ; Li, Lei ; Tang, Jinhai ; Xu, Di ; Sun, Yidan ; Shao, Xinyi ; Zhou, Honglei ; Shan, Liuqun ; Yang, Dawei ; Yan, Xueqin ; Yu, Qiang

Human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1-1000 nM) had potent and highly selective toxic effects on HER2⁺ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2⁺ breast cancer.

项与 Tarloxotinib Bromide 相关的新闻（医药）

2021-04-23

·Endpoints

April showers bring more biotechs to Nasdaq, as Rain and Impel bump 2021's total raise above $6B

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here. What’s that in the sky — is it a bird? Is it a plane? No, it’s another handful of biotech IPOs. Two more biotechs priced their public offerings late Thursday, coming just one day after Zymergen blew folks away with its $500 million pricing. This week’s winners are Rain Therapeutics and Impel Neuropharma, who raised $125 million and $80 million, respectively. Rain priced at $17 and Impel’s shares debuted at $15 apiece. Combined, the sector has now raised more than $6 billion among nearly three dozen debuts, according to the Endpoints News tally. That’s on pace to top last year’s record raise of $16.5 billion and 91 IPOs, per Nasdaq. Also on Thursday came the F-1 filing of Swiss biotech Molecular Partners, which is penciling in $100 million for its leap to Nasdaq. The company is already publicly traded in its home country. Rain stock price could bring company’s valuation to $427 million After a 2020 that led to a significant expansion of its pipeline, Rain Therapeutics has priced its IPO. The biotech that specializes in oncology has priced its 7,352,941 shares of its stock at $17 a share, and is expected to raise $125 million. In a release Monday, the company stated that price would command a market cap of $457 million. Rain’s pipeline tripled in a single week around Labor Day last year, when it licensed a research program from Drexel University and grabbed a Phase II-ready drug from Daiichi Sankyo. That program has become RAIN-32. That is the company’s lead program now, and should see the majority of IPO funds funneled toward it. RAIN-32 is a small molecule inhibitor of MDM2 taken orally to reduce tumors activity in liposarcoma and other solid tumors. In 2018, the company launched the experimental drug tarloxotinib with its $18 million in Series A fundraising. Last year, it raised $63 million. Rain will trade under the ticker $RAIN. — Josh Sullivan Impel announces IPO to launch migraine treatment Impel NeuroPharma is going public a little more than two years after its crossover raise, and Thursday, the company announced that it would be priced at $15 a share. Impel is expected to take home $80 million in proceeds with the public offering of 5,333,334 shares of its stock. The biotech from Seattle will use that money to commercially launch its migraine treatment Trudhesa, delivered through an upper nasal formulation of dihydroergotamine. The proceeds will also help its INP105 program, which is designed for treatment of agitation and aggression associated with autism spectrum disorder. This candidate, like many of the company’s drugs, is delivered to the brain through the nose, as it’s a nasal reformulation of olanzapine. Shares of Impel’s stock — which will be listed as $IMPL — will begin trading today. — Josh Sullivan Swiss biotech looking to hop across the pond with its protein therapies Molecular Partners is ostensibly seeking to capitalize on last month’s news that one of their antiviral programs will participate in an NIH-run Covid-19 trial. Molecular Partners teamed up with Novartis for the candidate, which is what they’re calling a “trispecific” DARPin antiviral known as ensovibep. Researchers will evaluate the antiviral as part of the NIH’s ACTIV-3, the hospitalized mild-to-moderate patient arm of their ACTIV protocol against Covid-19. If the medicine hits all its milestones, Novartis will be on the hook for up to $231 million. But Molecular Partners is also focusing on eye diseases, oncology and AML. The company has a Phase III program for wet AMD where they’ve partnered with Allergan/AbbVie and a lead cancer program for FAP-positive cancers in collaboration with Amgen. The biotech has three programs it expects to fund with its IPO: a Phase I trial for its second oncology program seeking to bind FAP and CD40, to complete a Phase I study for the second Novartis-partnered Covid-19 program known as MP0423, and to advance their liquid tumor portfolio in AML through Phase I as well. Once the IPO is closed, Molecular Partners will trade on the ticker $MOLN, which is also their Swiss ticker. — Max Gelman

合作小分子药物IPO

2021-04-07

·BioSpace

Rain Plans $100 Million IPO, Phase III Trial for Lead Precision Cancer Therapy

Newark, California-based cancer company Rain Therapeutics filed Friday for a $100 million IPO to advance its lead MDM2 inhibitor RAIN-32 into Phase III testing. The news comes months after the company closed a $63 million Series B and inlicensed RAIN-32 from Daiichi Sankyo. Rain licenses and develops precision cancer therapies. The new lead program, RAIN-32, previously completed Phase I testing in patients with solid tumors or lymphomas. The influx of cash will support a pivotal Phase III trial in liposarcoma, which Rain intends to launch this year, plus two more Phase II trials in solid tumors and intimal sarcoma, respectively. Preclinical data published by independent French researchers last year suggested MDM2 inhibitors had therapeutic potential for treating liposarcomas, where MDM2 amplification is common. MDM2 is an inhibitor of tumor-suppressive p53, a notoriously challenging drug target. Several companies are developing MDM2 inhibitors to act upstream of p53, with limited success, which Rain attributes to dose-limiting hematological toxicities. Last year, Roche ended development of its MDM2 inhibitor, idasanutlin, then in Phase II testing for patients with acute myeloid leukemia (AML). The most advanced anti-MDM2 therapy is APG-115, which Ascentage Pharma has in multiple Phase Ib/II trials for solid tumors and hematologic malignancies, plus a Phase II combination trial with checkpoint inhibitor Keytruda (pembrolizumab) for anti-PD-1 refractory or relapsed cancers. At least two other companies–Novartis and Aileron–also have MDM2 inhibitors in early clinical testing for several cancers. According to Rain, the safety and tolerability data from Daiichi Sankyo’s trial suggest RAIN-32 can be dosed longer than other MDM2-targeting programs in development. Rain also has a preclinical RAD52 inhibitor program, licensed from Drexel University in August 2020. RAD52 plays a role in DNA damage response and the company is exploring therapies for breast and ovarian cancers characterized by BRCA1/2 mutations. The company is aiming to select a lead clinical RAD52 inhibitor candidate in 2022. There are no known RAD52 inhibitors in clinical trials. As recently as last year, its previous lead candidate tarloxotinib, licensed from the University of Auckland, was in Phase II testing for patients with EGFR and ErbB Exon 20 insertion mutations in solid tumors. The company has not announced an end to the trial but tarloxotinib is not named in Rain’s Securities and Exchange Commission (SEC) forms or listed on the company’s website. Rain did not respond to a request for clarification in time for publication.

IPO

2016-09-02

·BioSpace

September is a Busy Month for 7 Biotechs

September 2, 2016 By Mark Terry , BioSpace.com Breaking News Staff September is going to be a busy month as seven biotech companies face big decisions by the U.S. Food and Drug Administration. Chris Lange, writing for 24/7 Wall Street, takes a look . 1. Achillion Pharmaceuticals Based in New Haven, Connecticut, Achillion Pharmaceuticals is focusing on hepatitis C drugs using complement factor D inhibitors. On September 23, it is presenting data from a Phase IIa trial that’s focused on safety, pharmacokinetics and efficacy of doublet and triplet regiments for genotype 1 hepatitis C virus (HCV). The trial is a joint deal with Alios BioPharma , a part of Johnson & Johnson . Achillion is currently trading for $8.22. 2. Amarin Corporation Dublin-based Amarin Corporation works to develop drugs for cardiovascular diseases. The company recently announced the completion of a study of 8,175 patients to evaluate if Vascepa cuts cardiovascular events in patients who are on statins, but still have elevated triglyceride levels and other cardiovascular risk factors. Enrollment closed in June. Although final data won’t happen until the second half of 2017 or later, interim analysis is expected this month. Amarin is currently trading at $2.84. 3. Array BioPharma Array BioPharma is headquartered in Boulder, Colorado. The company focuses on cancer treatments. The company announced yesterday that the FDA had accepted its New Drug Application (NDA) for binimetinib for NRAS-mutant melanoma. The PDUFA date is June 30, 2017. Array is currently trading for $3.48. 4. Mast Therapeutics Mast Therapeutics , based in San Diego, focuses on developing drugs for sickle cell disease and heart failure using its MAST (Molecular Adhesion and Sealant Technology) platform. The company is expected to announce topline data this month from its EPIC clinical trial of 388 patients with sickle cell disease. It is still enrolling patients for vepoloxamer’s EPIC-E trial. Mast Therapeutics is currently trading for $0.51. 5. Novavax Novavax , headquartered in Rockville, Maryland, uses recombinant nanoparticles and its Matrix-M adjuvant technology to develop vaccines. The company is expecting to report on its Phase III trial for respiratory syncytial virus (RSV) this month. Todd Campbell , writing for The Motley Fool, said, “If RSV-F is eventually approved, then Novavax believes its addressable market in the United States could exceed 100 million people in 2020. That has management thinking that peak annual sales for RSV-F could be north of $6 billion.” Novavax is currently trading for $6.845. 6. Threshold Pharmaceuticals South San Francisco-based 6. Threshold Pharmaceuticals is an oncology company. It currently is developing two drugs based on hypoxia-activated prodrug technology, evofosfamide and tarloxtinib bromide. The company plans to report this month on its Phase II proof of concept trial of tarloxotinib in hypoxic tumors. The company recently reported Phase III trial of evofosfamide, and continued collaborations on the drug in pancreatic neuroendocrine tumors (pNET), recurrent glioblastoma (GBM) and hepatocellular carcinoma (HCC). Threshold is currently trading for $1.18. 7. Vertex Pharmaceutical Vertex Pharmaceutical is based in Boston, and focuses on cystic fibrosis (CF) drugs. Its drug, Kalydeco had $632 million in sales in 2015, and its Orkambi gained approval in the U.S. and Europe. The company is planning to report this month on a Phase II trial of Orkambi in children with CF. The FDA approved Vertex’s request for a PDUFA Priority Review by the end of this month. Vertex is currently trading for $94.41.

临床3期临床2期上市批准申请上市优先审批

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14944

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
肺腺癌	临床2期	美国	Rain Oncology, Inc.	2022-03-07
KRAS G12C突变非小细胞肺癌	临床2期	美国	Rain Oncology, Inc.	2022-03-07
KRAS突变非小细胞肺癌	临床2期	美国	Rain Oncology, Inc.	2022-03-07
转移性非小细胞肺癌	临床2期	美国	Rain Oncology, Inc.	2019-03-13
转移性非小细胞肺癌	临床2期	加拿大	Rain Oncology, Inc.	2019-03-13
转移性非小细胞肺癌	临床2期	中国香港	Rain Oncology, Inc.	2019-03-13
非小细胞肺癌IIIB期	临床2期	美国	Rain Oncology, Inc.	2019-03-13
非小细胞肺癌IIIB期	临床2期	加拿大	Rain Oncology, Inc.	2019-03-13
非小细胞肺癌IIIB期	临床2期	中国香港	Rain Oncology, Inc.	2019-03-13
复发性非小细胞肺癌	临床2期	美国	Rain Oncology, Inc.	2019-03-13

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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


NCT05313009 (CTgov)	临床1/2期	KRAS突变非小细胞肺癌 \| 肺腺癌 \| KRAS G12C突变非小细胞肺癌 ... 更多	5	Tarloxotinib+Sotorasib (STAGE 1: SAFETY LEAD IN (n=6-18, depending on number of DLs explored))	窪製壓襯構膚製範製製 = 簾壓構艱艱蓋網壓顧範繭獵網醖觸窪繭廠艱鹹 (顧艱鹽願醖夢膚醖鹽糧, 獵艱顧廠獵鏇艱淵製觸 ~ 艱選糧餘餘艱願壓築膚) 更多	-	2025-12-16
NCT05313009 (CTgov)	临床1/2期	KRAS突变非小细胞肺癌 \| 肺腺癌 \| KRAS G12C突变非小细胞肺癌 ... 更多	5	Tarloxotinib+Sotorasib (STAGE 2: EFFICACY (n=12))	窪製壓襯構膚製範製製 = 餘遞蓋鹹範製窪衊衊齋繭獵網醖觸窪繭廠艱鹹 (顧艱鹽願醖夢膚醖鹽糧, 壓蓋醖築鹽鑰鏇鑰選簾 ~ 糧艱醖壓鬱築鏇網齋鑰) 更多	-	2025-12-16
NCT02449681 (Pubmed \| Invest New Drugs) 人工标引	临床2期	头颈部鳞状细胞癌	30	Tarloxotinib Bromide	積齋鹽鬱鹹觸憲構餘鏇(鹹膚膚艱鹹構網餘範醖) = 鹹鏇廠襯廠遞蓋選艱選獵餘淵願壓築衊獵構鏇 (鑰壓夢襯衊網願遞夢衊 ) 更多	不佳	2022-04-18
NCT03805841 (RAIN-701, ESMO2020) 人工标引	临床2期	实体瘤 \| 非小细胞肺癌 \| HER2突变型非小细胞肺癌 HER2 Mutation \| EGFR Exon 20 Insertion \| HER4 fusion ... 更多	23	tarloxotinib (EGFR Exon 20 insertion)	鏇鑰膚餘遞築廠糧壓繭(淵願選鬱齋顧膚積餘網) = 憲廠襯鏇顧繭鑰繭艱襯艱憲壓顧遞糧衊衊窪壓 (蓋遞鏇衊鏇願襯鏇網膚 ) 更多	积极	2020-09-18
NCT03805841 (RAIN-701, ESMO2020) 人工标引	临床2期		23	tarloxotinib (HER2 activating mutation)	餘淵繭築艱範壓衊積積(齋積選築鹽願獵網鬱醖) = 鏇構憲窪遞鑰簾遞選觸衊醖鹽糧憲簾衊鏇艱鬱 (衊網襯艱壓簾夢糧顧觸 ) 更多	积极	2020-09-18
ASCO2015	临床2期	非小细胞肺癌	-	TH-4000	鏇壓淵窪壓鬱襯衊鬱糧(範夢繭餘衊選鹽壓繭艱) = maintained for a week 襯繭壓齋製鹽範繭壓築 (窪範鬱願壓餘製膚繭鏇 )	-	2015-05-20