Delving into the Latest Updates on XL-999 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

EXEL-0999, XL 999

Target

AXL x FGFRs x FLT3 x c-Kit

Action

inhibitors, antagonists

Mechanism

AXL inhibitors(AXL receptor tyrosine kinase inhibitors), FGFRs antagonists(Fibroblast growth factor receptors antagonists), FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [5]

Active Indication-

Inactive Indication

Acute Promyelocytic LeukemiaAdvanced Malignant Solid NeoplasmMetastatic Colorectal Carcinoma+ [7]

Originator Organization

Exelixis, Inc.

Active Organization-

Inactive Organization

Symphony Evolution, Inc.

Exelixis, Inc.

License Organization

Exelixis, Inc.Symphony Evolution, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Cancer is a worldwide clinical and economic problem. Conventional approaches to treating cancer include surgery, radiotherapy, and cytotoxic chemotherapy as single modalities or as combined therapies. Recently, targeted therapies including antibodies and small molecule inhibitors have also demonstrated clinical benefit. It is now possible to study different genetic lesions involved in cancer types due to advances in genomic methodologies. The investigational drug in this study, XL999 inhibits multiple receptor tyrosine kinases, including VEGF receptor (VEGFR2/KDR), platelet derived growth factor receptors (PDGFRβ), fms-like tyrosine kinase receptor 3 (FLT3), fibroblast growth factor receptors (FGFR1, FGFR3), RET, and KIT, and thus, interferes with multiple cellular processes simultaneously and will likely have effects on the integrity of tumor neovasculature and angiogenesis. Together with the ability to induce a novel cell cycle arrest, the spectrum of activities that XL999 exhibits may reduce both tumor cell proliferation and angiogenesis in the clinic.
The rationale and purpose of this maintenance study is to allow a subject receiving clinical benefit from XL999 to continue treatment.

Start Date01 Apr 2010

Sponsor / Collaborator

University of Texas Health Science Center At San Antonio

NCT00955084

/ CompletedPhase 1

A Maintenance Study Evaluating the Long Term Safety of XL999 Administered Intravenously to Subjects With Advanced Malignancies Previously Enrolled in Other XL999 Studies

The primary objective of this study is to allow rollover of the two remaining subjects from the other XL999 studies to continue to receive XL999.
The secondary objectives of this study are as follows:
* To evaluate tumor response after long term repeat administration of XL999 in two subjects rolled over from other XL999 studies.
* To characterize the long term safety and tolerability of XL999 after repeat administration in two subjects rolled over from other XL999 studies.
* To characterize the long term effects of XL999 on cardiac function after repeat administration in two subjects rolled over from other XL999 studies.

Start Date01 Aug 2008

Sponsor / Collaborator

Symphony Evolution, Inc.

NCT00491699

/ TerminatedPhase 1

A Phase 1 Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL999 Administered Intravenously to Subjects With Non-Small-Cell Lung Cancer (NSCLC)

The purpose of this study is to determine the safest dose of XL999 and how well subjects with Non-Small-Cell Lung Cancer tolerate XL999. XL999 is a small molecule inhibitor of multiple kinases including VEGFR, PDGFR, FGFR, FLT-3, and Src, which are involved in tumor cell growth, formation of new blood vessels (angiogenesis), and metastasis.

Start Date01 Aug 2007

Sponsor / Collaborator

Symphony Evolution, Inc.

100 Clinical Results associated with XL-999

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100 Translational Medicine associated with XL-999

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100 Patents (Medical) associated with XL-999

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3

Literatures (Medical) associated with XL-999

07 Oct 2025·Microbiology Spectrum

Intratumoral core microbiota predicts prognosis and therapeutic response in gastrointestinal cancers

Article

Author: Chen, Yue ; Wei, Dongsheng ; Liu, Jia ; Liu, Xingzhong

ABSTRACT:

Microbial communities residing in tumors constitute a critical component of the tumor microenvironment, particularly in gastrointestinal cancers arising from mucosal sites. However, the relationship between microbiota and oncogenesis, as well as its clinical applications, remains underexplored. Here, we performed a comprehensive analysis of the tumor microbiome across six gastrointestinal cancer types and identified a core microbiota composed of 15 bacterial genera associated with patient prognosis. Using bacterial abundance data, we developed a microbiota-based prognostic model to calculate a “risk score.” Patients with high-risk scores exhibited poorer prognosis and increased metastatic potential, driven by the activation of tumor metastasis-related signaling pathways, including epithelial-mesenchymal transition, angiogenesis, KRAS, and TGFβ signaling. Furthermore, the model predicted sensitivity to anti-cancer drugs, identifying XL999 and tandutinib as potential targeted therapies for high-risk patients. The core microbiota is also linked to host immunity; patients with high-risk scores were less likely to benefit from immunotherapy. Taken together, these findings highlight the potential of a microbiota-based prognostic model to enhance cancer diagnostics, inform therapeutic decision-making, and advance personalized medicine for gastrointestinal cancers.

IMPORTANCE:

Intratumoral microbiota influence cancer progression, yet their prognostic potential remains underutilized. This study identifies a core microbiota of 15 bacterial genera associated with survival in gastrointestinal cancers and develops a microbiota-based prognostic model. Unlike traditional gene-based models, this approach stratifies patients by microbial signatures, linking high-risk scores to enhanced metastasis via epithelial-mesenchymal transition, angiogenesis, and KRAS signaling. Additionally, we identify XL999 and tandutinib as potential therapies for high-risk patients and reveal that microbiota composition correlates with immunotherapy response. By integrating microbiome profiling into cancer prognosis and treatment selection, this study offers a novel strategy for precision oncology, advancing microbial biomarkers for risk assessment, drug selection, and personalized immunotherapy.

15 Jul 2011·Cancer researchQ1 · MEDICINE

VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer

Q1 · MEDICINE

Article

Author: Falcón, Beverly ; Williamson, Casey W. ; Yao, Li-Chin ; McDonald, Donald M. ; Aftab, Dana T. ; You, Weon-Kyoo ; Hashizume, Hiroya ; Sennino, Barbara

Abstract:

Angiogenesis inhibitors that block VEGF receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTK). XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small-molecule inhibitors that potently block multiple RTKs, including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 with those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but treatment with XL880 or XL184 eliminated approximately 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis. Cancer Res; 71(14); 4758–68. ©2011 AACR.

01 Mar 2007·Methods and findings in experimental and clinical pharmacology

Gateways to clinical trials.

Author: Bayes, Miriam

Agomelatine, AGRO-100, AIDSVAX gp120 B/E, alfimeprase, aliskiren fumarate, ALVAC vCP1452, alvocidib hydrochloride, ambrisentan, AME-527, AN-0128, apadenoson, ARRY-142886, asenapine maleate, axitinib, azimilide hydrochloride; Belimumab, bevacizumab, biolimus A9, BiovaxID, bryostatin 1; Cannabidiol, celgosivir, CG-1940/CG-8711, CKD-501, collagen-PVP, CpG-10101, CTL-102, CTL-102/CB-1954; D-4F, darusentan, dexverapamil, DNA influenza vaccine, dronabinol/cannabidiol, dronedarone hydrochloride; Eculizumab, edodekin alfa, edotecarin, enzastaurin hydrochloride; Fingolimod hydrochloride; Golimumab; HBV-DNA vaccine, hyaluronic acid; I-131 ch-TNT-1/B, imatinib mesylate, inhaled insulin, ipilimumab, ispinesib mesylate, i.v. gamma-globulin; KU-59436; Lapaquistat; Mapatumumab, MC-1, MC-1/lisinopril, mepolizumab; Nibentan, nilotinib, Nobori, NV1FGF; Ocrelizumab; Paclimer, pagoclone, paliperidone, PC-515, PHA-794428, phosphostim, PPI-2458, prasugrel, PTC-299; Renzapride hydrochloride, Reolysin, reslizumab, revaprazan hydrochloride, rivaroxaban, romidepsin, rubitecan, ruboxistaurin mesilate hydrate; Sapacitabine, SarCNU, ST-1859, sunitinib malate; Tanespimycin, temsirolimus, tgAAC-94, TGN-255, ticagrelor, tipifarnib, tolvaptan, tretazicar, TRU-015; Upgrade varicella vaccine, Ushercell; Vernakalant hydrochloride, verpasep caltespen, VNP-40101M, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VX-001; XL-647, XL-820, XL-880, XL-999.

100 Deals associated with XL-999

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Promyelocytic Leukemia	Phase 2	United States	Symphony Evolution, Inc.	01 May 2006
Relapse multiple myeloma	Phase 2	United States	Symphony Evolution, Inc.	01 Feb 2006
Recurrent ovarian cancer	Phase 2	United States	Symphony Evolution, Inc.	01 Jan 2006
Metastatic Colorectal Carcinoma	Phase 2	United States	Symphony Evolution, Inc.	01 Dec 2005
Metastatic Renal Cell Carcinoma	Phase 2	United States	Symphony Evolution, Inc.	01 Dec 2005
Non-Small Cell Lung Cancer	Phase 2	United States	Symphony Evolution, Inc.	01 Dec 2005
Recurrent Non-Small Cell Lung Cancer	Phase 2	United States	Symphony Evolution, Inc.	01 Dec 2005
Non-small cell lung cancer stage IIIB	Phase 1	United States	Symphony Evolution, Inc.	01 Aug 2007
Advanced Malignant Solid Neoplasm	Phase 1	United States	Symphony Evolution, Inc.	01 Nov 2004
Neoplasms	Phase 1	United States	Exelixis, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2007	Phase 2	Acute Myeloid Leukemia \| Recurrent ovarian cancer \| Multiple Myeloma ... View more	79	XL999	vjiddawqbs(zgxhlhccjt) = mkfviygjxd kmaiqvqlky (ujdzqhwlcd )	-	20 Jun 2007
ASCO2006	Phase 1	Advanced Malignant Solid Neoplasm	15	XL999 2.4 mg/kg	mxprcdwboh(xftqdsfsad) = csozowpsua cuzaweyfmh (jlsgbipoxv ) View more	-	20 Jun 2006