Delving into the Latest Updates on Alisertib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Alisertib (USAN), Alisertib Sodium, Alsertib

+ [1]

Target

Aurora A

Mechanism

Aurora A inhibitors(Serine/threonine-protein kinase Aurora-A inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Breast cancer recurrentHormone receptor positive HER2 negative breast cancerExtensive stage Small Cell Lung Cancer+ [5]

Inactive Indication

Acinar Cell CarcinomaAcute Myeloid LeukemiaAdenocarcinoma of prostate+ [58]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Millennium Pharmaceuticals, Inc.US Oncology Research LLCTakeda Pharmaceuticals U.S.A., Inc.

+ [1]

Inactive Organization

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC27H20ClFN4O4

InChIKeyZLHFILGSQDJULK-UHFFFAOYSA-N

CAS Registry1028486-01-2

PUMA-ALI-1201 is a randomized, dose optimization, multicenter, Phase 2 study of alisertib administered in combination with endocrine therapy in participants with pathology-confirmed HR-positive/HER2-negative metastatic breast cancer (MBC) following progression on or after at least two prior lines of endocrine therapy in the recurrent or metastatic setting. This study is intended to evaluate the optimal alisertib dose administered in combination with the selected endocrine therapy. The study is also planned to evaluate the efficacy, safety, and pharmacokinetics of alisertib in combination with endocrine and to identify the biomarker-defined subgroup(s) that may benefit most from combined alisertib and endocrine therapy.

Start Date31 Dec 2024

Sponsor / Collaborator

Puma Biotechnology, Inc.

NCT06095505 / RecruitingPhase 2

A Phase 2 Study of Alisertib in Patients With Extensive Stage Small Cell Lung Cancer

PUMA-ALI-4201 is a Phase 2 study evaluating alisertib monotherapy in patients with pathologically-confirmed small cell lung cancer (SCLC) following progression on or after treatment with one platinum-based chemotherapy and anti-PD-L1 immunotherapy agent. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to two prior lines of therapy. This study is intended to identify the biomarker-defined subgroup(s) that may benefit most from alisertib treatment and to evaluate the efficacy, safety, and pharmacokinetics of alisertib.

Start Date08 Feb 2024

Sponsor / Collaborator

Puma Biotechnology, Inc.

NCT04555837 / Active, not recruitingPhase 1/2IIT

A Phase I-II, Open Label Study Evaluating the Safety and Efficacy of Alisertib and Pembrolizumab in Patients With Rb-Deficient Head and Neck Squamous Cell Carcinomas

This phase I/II trial investigates the best dose and effect of alisertib in combination with pembrolizumab in treating patients with Rb-deficient head and neck squamous cell cancer. Alisertib may help block the growth of cancer.. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving alisertib in combination with pembrolizumab may help control Rb-deficient head and neck squamous cell cancer. HPV positive head and neck cancers are Rb-deficient.

Start Date15 Sep 2020

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with Alisertib

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100 Translational Medicine associated with Alisertib

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100 Patents (Medical) associated with Alisertib

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335

Literatures (Medical) associated with Alisertib

01 Sep 2024·Neoplasia

Aurkin-A, a TPX2-Aurora A small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma

Article

Author: Conway, Patrick J ; Kovalskyy, Dmytro ; De La Peña Avalos, Bárbara ; Dao, Jonathan ; Mahadevan, Daruka ; Dray, Eloise ; Montagnino, Sebastian

Chemotherapy induced polyploidy is a mechanism of inherited drug resistance resulting in an aggressive disease course in cancer patients. Alisertib, an Aurora Kinase A (AK-A) ATP site inhibitor, induces cell cycle disruption resulting in polyaneuploidy in Diffuse Large B Cell Lymphoma (DLBCL). Propidium iodide flow cytometry was utilized to quantify alisertib induced polyploidy in U2932 and VAL cell lines. In U2932 cells, 1µM alisertib generated 8n+ polyploidy in 48% of the total cell population after 5 days of treatment. Combination of Aurkin A an AK-A/TPX2 site inhibitor, plus alisertib disrupted alisertib induced polyploidy in a dose-dependent manner with associated increased apoptosis. We generated a stable FUCCI U2932 cell line expressing Geminin-clover (S/G₂/M) and cdt1-mKO (G₁), to monitor cell cycle progression. Using this system, we identified alisertib induces polyploidy through endomitosis, which was eliminated with Aurkin A treatment. In a VAL mouse xenograft model, we show polyploidy generation in alisertib treated mice versus vehicle control or Aurkin A. Aurkin A plus alisertib significantly reduced polyploidy to vehicle control levels. Our in vitro and in vivo studies show that Aurkin A synergizes with alisertib and significantly decreases the alisertib dose needed to disrupt polyploidy while increasing apoptosis in DLBCL cells.

01 Jul 2024·Translational Oncology

Aurora kinase A inhibition plus Tumor Treating Fields suppress glioma cell proliferation in a cilium-independent manner

Article

Author: Sarkisian, Matthew R ; Khoshbouei, Habibeh ; Mallinger, Julianne C ; Tian, Jia ; Ling, Dahao ; Shi, Ping ; Deleyrolle, Loic P ; Lin, Min

Tumor Treating Fields (TTFields) extend the survival of glioblastoma (GBM) patients by interfering with a broad range of tumor cellular processes. Among these, TTFields disrupt primary cilia stability on GBM cells. Here we asked if concomitant treatment of TTFields with other agents that interfere with GBM ciliogenesis further suppress GBM cell proliferation in vitro. Aurora kinase A (AURKA) promotes both cilia disassembly and GBM growth. Inhibitors of AURKA, such as Alisertib, inhibit cilia disassembly and increase ciliary frequency in various cell types. However, we found that Alisertib treatment significantly reduced GBM cilia frequency in gliomaspheres across multiple patient derived cell lines, and in patient biopsies treated ex vivo. This effect appeared glioma cell-specific as it did not reduce normal neuronal or glial cilia frequencies. Alisertib-mediated depletion of glioma cilia appears specific to AURKA and not AURKB inhibition, and attributable in part to autophagy pathway activation. Treatment of two different GBM patient-derived cell lines with TTFields and Alisertib resulted in a significant reduction in cell proliferation compared to either treatment alone. However, this effect was not cilia-dependent as the combined treatment reduced proliferation in cilia-depleted cell lines lacking, ARL13B, or U87MG cells which are naturally devoid of ARL13B⁺ cilia. Thus, Alisertib-mediated effects on glioma cilia may be a useful biomarker of drug efficacy within tumor tissue. Considering Alisertib can cross the blood brain barrier and inhibit intracranial growth, our data warrant future studies to explore whether concomitant Alisertib and TTFields exposure prolongs survival of brain tumor-bearing animals in vivo.

04 Jun 2024·Molecular Cancer Therapeutics

Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus

Article

Author: Zhuang, Hong ; Tsai, Chia-Hua ; Chi, Ya-Hui ; Chen, Ching-Ping ; Chen, Chiung-Tong ; Wang, Wan-Ping ; Huang, Chen-Lung ; Hsieh, Tsung-Chih ; Ke, Yi-Yu ; Wu, Mine-Hsine ; Chang, Chun-Ping ; Chen, Yen-Ting ; Wang, Jing-Ya ; Yeh, Teng-Kuang ; Chen, Yan-Fu ; Chen, Ya-Ping

AbstractAurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC.

56

News (Medical) associated with Alisertib

05 Nov 2024

·www.businesswire.com

Puma Biotechnology Reports Inducement Awards Under Nasdaq Listing Rule 5635(c)(4)

LOS ANGELES--( BUSINESS WIRE )--Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced that on November 4, 2024, the Compensation Committee of Puma’s Board of Directors approved the grant of an inducement restricted stock unit award covering 5,625 shares of Puma common stock to one new non-executive employee. The award was granted under Puma’s 2017 Employment Inducement Incentive Award Plan, which was adopted on April 27, 2017 and provides for the granting of equity awards to new employees of Puma. The restricted stock unit award vests over a three-year period, with one-third of the shares underlying the award vesting on the first anniversary of the award’s vesting commencement date, November 1, 2024, and one-sixth of the shares underlying the award vesting on each six-month anniversary of the vesting commencement date thereafter, subject to continued service. The award was granted as an inducement material to the new employee entering into employment with Puma, in accordance with Nasdaq Listing Rule 5635(c)(4). About Puma Biotechnology Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc. In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA™-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer.

Drug ApprovalLicense out/inPhase 2

24 Oct 2024

·www.biospace.com

Puma Biotechnology to Host Conference Call to Discuss Third Quarter Financial Results

LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NASDAQ:PBYI), a biopharmaceutical company, will host a conference call at 1:30 p.m. PST/4:30 p.m. EST on Thursday, November 7, 2024, following the release of its third quarter 2024 financial results. The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the “Puma Biotechnology Conference Call.” A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at . A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days. About Puma Biotechnology Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc. In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA™-Lung 1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer. Further information about Puma Biotechnology may be found at . Contacts Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc., +1 424 248 6500 info@pumabiotechnology.com ir@pumabiotechnology.com David Schull or Olipriya Das, Russo Partners, +1 212 845 4200 david.schull@russopartnersllc.com olipriya.das@russopartnersllc.com

Drug ApprovalLicense out/inPhase 2Phase 1Financial Statement

18 Jul 2024

·www.businesswire.com

Puma Biotechnology to Host Conference Call to Discuss Second Quarter 2024 Financial Results

LOS ANGELES--( BUSINESS WIRE )--Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, will host a conference call at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, August 1, 2024, following the release of its second quarter 2024 financial results. The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the “Puma Biotechnology Conference Call.” A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at https://www.pumabiotechnology.com . A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days. About Puma Biotechnology Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral) in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc. In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, an investigational, selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA™-Lung 1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer. Further information about Puma Biotechnology may be found at https://www.pumabiotechnology.com .

Drug ApprovalLicense out/inPhase 2Phase 1Financial Statement

100 Deals associated with Alisertib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10085	Alisertib	-	DB05220

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Peripheral T-cell lymphoma unspecified refractory	Preclinical	NL	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	GB	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	DK	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	PR	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	PE	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	RO	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	AT	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	BE	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	EG	Millennium Pharmaceuticals, Inc.	11 Jun 2012
Peripheral T-cell lymphoma unspecified refractory	Preclinical	IL	Millennium Pharmaceuticals, Inc.	11 Jun 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02860000 (TBCRC041, CTgov)	Phase 2	Locally advanced breast cancer \| Hormone refractory breast cancer \| Metastatic breast cancer \| Invasive Mammary Carcinoma \| Breast Cancer 3	96	Laboratory Biomarker Analysis+Alisertib (Arm I (Alisertib))	hhkesqpxhx(fpogybvqon) = oqushxhuhh jqxtclcxny (rlvdficlcy, kssftcxttc - ongruiyrea) View more	-	18 Oct 2024
				Laboratory Biomarker Analysis+Alisertib+Fulvestrant (Arm II (Alisertib, Fulvestrant))	hhkesqpxhx(fpogybvqon) = bqburaqsnu jqxtclcxny (rlvdficlcy, pdqdsomxlg - dyjdurnblu) View more
NCT02187991 (CTgov)	Phase 2	Metastatic breast cancer	169	Paclitaxel (ER+/HER2- Paclitaxel Alone)	hlghnalynk(yecamzagfr) = twuvehbuwr jedpmyszqf (bonkrzhnnx, citazhposx - oceyminswu) View more	-	09 Oct 2024
				Alisertib+Paclitaxel (ER+/HER2- Paclitaxel Plus Alisertib)	hlghnalynk(yecamzagfr) = lujrouepso jedpmyszqf (bonkrzhnnx, rzvisyyipa - knemexkwvn) View more
NCT04085315 (phase I/Ib study, ASCO2024) Manual	Phase 1	EGFR Mutation Lung Cancer EGFR	21	alisertib+osimertinib	(wtrejupknf) = neutropenia (42.9%), anemia (42.9%), and diarrhea (38.1%) wjxodxnqan (duqmmlpqel )	Positive	24 May 2024
NCT02860000 (TBCRC041, ASCO2024)	Phase 2	Metastatic breast cancer ESR1 \| PIK3CAmutation \| AKT1 ... View more	91	Alisertib + Fulvestrant	(zazlzxkrar): HR = 1.8 (95% CI, 1.1 - 2.9), P-Value = 0.014	Positive	24 May 2024
				Alisertib
NCT02187991 (ASCO2023)	Phase 2	HER2-negative breast cancer	96	Alisertib+Paclitaxel	(xiuarfxvan) = cmktyoexkz vuxnojinap (meqzzbndaz )	Positive	31 May 2023
NCT02860000 (Pubmed)	Phase 2	Advanced breast cancer CDK 4/6i	91	Alisertib	(hbyvkquqjd) = dzkumndrsk skxaasfuwq (yavkbqwqzc, 29.0% - 54.5%) View more	-	09 Mar 2023
				Alisertib + Fulvestrant	(hbyvkquqjd) = mnwbgvcjit skxaasfuwq (yavkbqwqzc, 18.0% - 42.0%) View more
NCT02293005 (CTgov)	Phase 2	Mesothelioma, Malignant	28	Alisertib	(xlpwvjpgzv) = fkzcdmjtgj fuqglrrlwd (jjgqdwjhpl, auhndhaayi - spfruphgyx) View more	-	04 Oct 2022
NCT01924260 (Pubmed) Manual	Phase 1	HR-positive/HER2-low Solid Tumors \| Pancreatic Cancer	26	Alisertib+Gemcitabine	(hryqrcgnub) = xcihujuuyj qsyexyuwcg (grsfiswrvt, 2.1 - 4.5) View more	Positive	30 Jul 2022
NCT02114229 (SJATRT, Pubmed) Manual	Phase 2	Rhabdoid Tumor of the CNS	30	alisertib	(zdixblqwwx) = dchwhacrpo kgckjcjezl (sivgweboha, 5.6) View more	Negative	02 Jun 2022
NCT04479306 (ASCO2022)	Phase 1	Recurrent Non-Small Cell Lung Cancer	40	Osimertinib 80 mg daily + Alisertib 20 mg, 30 mg, and 40 mg daily	(xffdeqylfc) = Biomarker analysis is ongoing to identify the molecular determinants of response and resistance to sapasertib uagrgfkuud (bkwshokxln ) View more	-	02 Jun 2022
				Osimertinib 80 mg daily + Sapanisertib 2 mg and 3 mg daily