Delving into the Latest Updates on Poziotinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Poziotinib hydrochloride, 泊齐替尼, HM-781-36B

+ [6]

Target

EGFR exon 20 x HER2 exon 20 x HER4

Action

inhibitors, antagonists

Mechanism

EGFR exon 20 inhibitors(EGFR exon 20 Mutation inhibitors), HER2 exon 20 inhibitors(ERBB2 Exon 20 Mutation inhibitors), HER4 antagonists(Receptor tyrosine-protein kinase erbB-4 antagonists)

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders

Active Indication

Head and Neck NeoplasmsLung CancerStomach Cancer

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaAdvanced Malignant Solid NeoplasmEGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma+ [12]

Originator Organization

Hanmi Pharmaceutical Co., Ltd.

Active Organization

Luye Pharma Group Ltd.

Hanmi Pharmaceutical Co., Ltd.

Spectrum Pharmaceuticals, Inc.

Inactive Organization

The University of Texas MD Anderson Cancer Center

License Organization

Hanmi Pharmaceutical Co., Ltd.

Luye Pharma AG

Spectrum Pharmaceuticals, Inc.

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

RegulationFast Track (United States)

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Structure/Sequence

Molecular FormulaC23H21Cl2FN4O3

InChIKeyLPFWVDIFUFFKJU-UHFFFAOYSA-N

CAS Registry1092364-38-9

This phase II trial tests whether poziotinib and ramucirumab work to shrink tumors in patients with EGFR Exon 20 gene mutant stage IV non-small cell lung cancer. Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ramucirumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving poziotinib and ramucirumab may help to control the disease.

Start Date16 Jun 2021

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

NCT04981704

/ CompletedPhase 1

A Three-Part, Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of Itraconazole, Phenytoin, and Paroxetine on the Single-Dose Pharmacokinetics of Poziotinib in Healthy Adult Subjects

The purpose of the study is to evaluate the effect of multiple-doses of itraconazole, phenytoin and paroxetine on the single-dose pharmacokinetics (PK) of poziotinib in healthy adult participants.

Start Date08 Apr 2021

Sponsor / Collaborator

Spectrum Pharmaceuticals, Inc.

100 Clinical Results associated with Poziotinib

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100 Translational Medicine associated with Poziotinib

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100 Patents (Medical) associated with Poziotinib

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148

Literatures (Medical) associated with Poziotinib

01 Jan 2026·Journal of Thoracic Oncology

Loss of Payload Sensitivity and Other Mechanisms of Resistance to T-DXd in HER2-Mutant NSCLC: Implications for Subsequent Responsiveness to HER2 TKIs

Article

Author: Kittler, Ralf ; Heymach, John V ; Jun, Soyeong ; Esfahani, Mohammad Shahrokh ; Kumar, Ashwani ; Kang, Xiaoman ; Shibata, Yuji ; Poteete, Alissa ; Wang, Jing ; Wakelee, Heather ; Mutter, Jurik ; Huo, Xiaofang ; Ren, Xiaoyang ; Sugio, Takeshi ; Wang, Rui ; Oguchi, Kei ; Le, Xiuning ; Soltys, Scott ; Diehn, Maximilian ; Liu, Ximeng ; Tran, Hai ; Minamiguchi, Kazuhisa ; Almanza, Diego ; Nilsson, Monique B ; Huang, Qian ; Yu, Xiaoxing ; Alizadeh, Ash A ; Xi, Yuanxin ; He, Junqin ; Hong, Lingzhi ; Weipert, Caroline M ; Moran, Cesar

INTRODUCTION:

Effective therapies are needed for patients with NSCLC with HER2-mutant tumors who progress on the HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd), a standard-of-care treatment. A greater understanding of mechanisms mediating acquired T-DXd resistance and whether these tumors could benefit from HER2 tyrosine kinase inhibitors (TKIs) is needed.

METHODS:

Using preclinical models of acquired T-DXd resistance, LentiMutate scanning mutagenesis, and clinical analyses, we investigated mechanisms mediating acquired resistance to T-DXd and assessed the impact of each of these resistance mechanisms on cross-resistance to alternative HER2-targeting approaches.

RESULTS:

We determined that acquired resistance to T-DXd could occur through multiple mechanisms including payload resistance which could be mediated by SFLN11 loss and copy number gains in the efflux pump ABCC1/MRP1. Moreover, T-DXd resistance could be mediated by secondary HER2 extracellular mutations in domain IV, the trastuzumab binding site. Tumor cells with acquired payload resistance or domain IV mutations maintained HER2 signaling and remained sensitive to HER2 TKIs, including zongertinib or poziotinib. Likewise, patients with HER2-mutant NSCLC treated with poziotinib demonstrated similar response rates regardless of prior T-DXd.

CONCLUSIONS:

In patients with HER2-mutant NSCLC, loss of HER2 is not a universal mechanism of T-DXd resistance. Collectively, these data highlight multiple mechanisms of resistance to T-DXd that do not result in loss of HER2 TKI responsiveness.

28 Jul 2025·Cureus Journal of Medical Science

Targeted Therapy in HER2 Exon 20-Mutant Non-small Cell Lung Cancer With Leptomeningeal Disease: A Case-Based Approach to Treatment Decision-Making

Article

Author: Elzaafarany, Osama

A rare and clinically challenging case of leptomeningeal disease (LMD) secondary to HER2-mutated non-small cell lung cancer (NSCLC), marked by both exon 20 insertion and gene amplification, is presented. In the absence of LMD-specific therapeutic guidelines for HER2-driven NSCLC, treatment was initiated with trastuzumab deruxtecan (Enhertu), based on extrapolated evidence from clinical trials in systemic NSCLC and HER2-positive breast cancer with central nervous system involvement. The patient, a 69-year-old woman with good performance status, developed LMD following prior systemic therapy and local CNS treatments. MRI and CSF cytology confirmed the diagnosis. Given the lack of approved therapies for HER2-mutant NSCLC with LMD, the treatment strategy was informed by available clinical data and supporting literature on the CNS activity of Enhertu. Other options such as poziotinib and zongertinib were considered but not pursued. This case underscores the urgent need for inclusive clinical trials addressing CNS complications in molecularly defined NSCLC and demonstrates the real-world application of precision oncology beyond trial populations.

15 Jul 2025·Cancer Research and Treatment

Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy

Article

Author: Hye Ryun Kim ; Sang-Gon Park ; Keun-Wook Lee ; Yun-Gyoo Lee ; Sung-Bae Kim ; Hwan Jung Yun ; Sangwoo Kim ; Seung Taek Lim ; Seong Hoon Shin ; Min Kyoung Kim ; Hyun Woo Lee ; Eun Joo Kang ; Yoon Hee Choi ; Shinwon Hwang ; Jong-Kwon Choi

Purpose Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.Materials and Methods We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).Results TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).Conclusion TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

47

News (Medical) associated with Poziotinib

12 Aug 2025

·www.prnewswire.com

Spectrum Pharmaceuticals (SPPI) Lead Plaintiff Process Re-Opened, Investors with Losses Urged to Contact Hagens Berman Before September 24, 2025 Deadline

SPPI Investors with Losses Encouraged to Contact Hagens Berman SAN FRANCISCO, Aug. 12, 2025 /PRNewswire/ -- On August 4, 2025, the court overseeing the pending securities class action styled Christiansen v. Spectrum Pharmaceuticals, Inc., et al., No. 1:22-cv-10292 (S.D.N.Y.) re-opened the lead plaintiff process and set September 24, 2025 as the deadline for investors to seek appointment as the new lead plaintiff. The Lead Plaintiff would seek to represent investors who purchased Spectrum common stock between March 17, 2022 and September 22, 2022. National shareholders rights firm Hagens Berman continues to investigate the lawsuit's legal claims and urges Spectrum investors who suffered substantial losses to submit your losses now. The firm also encourages persons with knowledge who may be able to assist in the investigation to contact its attorneys. Class Period: Mar. 17, 2022 – Sept. 22, 2022 Lead Plaintiff Deadline: Sept. 24, 2025 Visit: Contact the Firm Now: [email protected] 844-916-0895 The Spectrum Pharmaceuticals (SPPI) Securities Class Action: The litigation is focused on the propriety of Spectrum's statements about its development of poziotinib ("pozi"), a drug under investigation for the treatment of previously treated patients (so-called second-line patients) with non-small cell lung cancer ("NSCLC") with certain genetic mutations. More specifically, the complaint alleges that Spectrum repeatedly assured investors of positive safety and efficacy data from its pozi phase 2 clinical trial and that it initiated the required confirmatory phase 3 while omitting crucial information. Investors began to learn the truth on September 20, 2022, when the FDA Oncologic Drugs Advisory Committee released a briefing document ("ODAC") which disclosed both negative data on the safety and efficacy of pozi AND that Spectrum had not enrolled any patients in the required confirmatory phase 3 trial. Then, during the September 22 ODAC meeting, the committee overwhelmingly voted against pozi for accelerated approval. These events drove the price of Spectrum shares crashing lower. "We're continuing to investigate the legal claims pending against Spectrum and, in the wake of the District Court's order re-opening the lead plaintiff process, are strongly encouraging investors to contact us about moving to be appointed the new lead plaintiff," said Reed Kathrein, the Hagens Berman partner leading the investigation. If you invested in Spectrum and have substantial losses, or have knowledge that may assist the firm's investigation, submit your losses now » If you'd like more information and answers to frequently asked questions about the Spectrum Pharmaceuticals case and our investigation, read more » Whistleblowers: Persons with non-public information regarding Spectrum should consider their options to help in the investigation or take advantage of the SEC Whistleblower program. Under the new program, whistleblowers who provide original information may receive rewards totaling up to 30 percent of any successful recovery made by the SEC. For more information, call Reed Kathrein at 844-916-0895 or email [email protected]. About Hagens Berman Hagens Berman is a global plaintiffs' rights complex litigation firm focusing on corporate accountability. The firm is home to a robust practice and represents investors as well as whistleblowers, workers, consumers and others in cases achieving real results for those harmed by corporate negligence and other wrongdoings. Hagens Berman's team has secured more than $2.9 billion in this area of law. More about the firm and its successes can be found at hbsslaw.com. Follow the firm for updates and news at @ClassActionLaw. SOURCE Hagens Berman Sobol Shapiro LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 3

31 May 2023

·www.fiercebiotech.com

Yuhan makes $325M cancer bet to challenge Boehringer, Takeda

JIN-A04 will slot into a pipeline led by the EGFR tyrosine kinase inhibitor lazertinib. Yuhan Corporation has bought its way into a cancer space targeted by Boehringer Ingelheim and Takeda, wagering up to $325 million to get its hands on a preclinical HER2 tyrosine kinase inhibitor (TKI). The oral drug candidate, which Korea’s Yuhan is licensing from its compatriot J INTS BIO, is designed for use in non-small cell lung cancer (NSCLC) patients with HER2 exon 20 insertion mutations. Around 3% of NSCLC patients have HER2 mutations, and around 90% of those mutations are exon 20 insertions. The potential to improve outcomes in that subset of patients has attracted a clutch of drug developers. Spectrum Pharmaceuticals sought FDA approval for poziotinib in NSCLC harboring HER2 exon 20 insertion mutations late in 2021 but deprioritized the program after receiving a rejection notice last year. Rival drug candidates remain in active clinical development, with Boehringer studying BI 1810631 in a phase 1 trial and Takeda securing approval two years ago for mobocertinib, a TKI that targets EGFR and HER2 insertions. Flanked by deep-pocketed rivals with more advanced programs, J INTS BIO has pitched its TKI candidate as a potential best-in-class molecule. The claim, which is backed by in vitro and in vivo models showing it is potent against HER2 exon 20 insertions, has helped the Korean biotech land a deal for the therapy. Yuhan has taken the other side of the agreement. The Korean drugmaker, which owns a 15% stake in J INTS BIO, is paying $1.9 million upfront as part of a deal worth up to $325 million to secure rights to the JIN-A04 drug candidate. At Yuhan, JIN-A04 will slot into a pipeline led by the EGFR TKI lazertinib. Johnson & Johnson paid Yuhan $50 million upfront and committed to $1.2 billion in milestones for rights to the small molecule outside of Korea in 2018. Yuhan went on to launch the drug in Korea, under the Leclaza name, as a second-line treatment for NSCLC while continuing to study the molecule in other settings.

Drug ApprovalPhase 1License out/inOligonucleotideAccelerated Approval

25 Apr 2023

·firstwordpharma.com

Spectrum to be swallowed by Assertio

Spectrum Pharmaceuticals agreed to be acquired by Assertio, less than six months after failing to secure FDA approval of poziotinib for lung cancer patients harbouring HER2 exon 20 insertion mutations. The deal announced Tuesday includes a stock component worth $248 million to Spectrum's shareholders, as well as contingent value rights (CVRs) totalling $43 million linked to the company's sole marketed drug Rolvedon (eflapegrastim-xnst).Following the rejection of poziotinib, Spectrum cut its R&D workforce by approximately 75%, having slashed 30% of its staffing numbers earlier last year to focus on Rolvedon. The long-acting G-CSF product is authorised in the US for adults with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant febrile neutropenia.Tom Riga, Spectrum's CEO, suggested that the merger "will position us to accelerate Rolvedon's launch," with the product having generated sales of $10.1 million in its first quarter on the market. Assertio chief executive Dan Peisert said "we intend to retain the majority of Spectrum's commercial infrastructure, which we believe is synergistic to our digital non-personal platform, deploying these complementary dual channels to support clinical messaging, reimbursement education and Rolvedon awareness to further aid and accelerate its launch."The companies noted that the first CVR worth $0.10 per share will be payable upon Rolvedon sales achieving $175 million in 2024, with another $0.10 due if the product's revenue reaches $225 million the following year. Assertio indicated that Rolvedon's intellectual property protection is anticipated to extend through 2036.Following closing of the transaction, which is expected in the third quarter, Assertio will own approximately 65% of the combined company, with Spectrum shareholders owning the remaining 35%.

Drug ApprovalAcquisition

100 Deals associated with Poziotinib

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External Link

KEGG	Wiki	ATC	Drug Bank
D12229 D12230	Poziotinib	-	DB12114

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	NDA/BLA	United States	Spectrum Pharmaceuticals, Inc.	-
Advanced Lung Non-Small Cell Carcinoma	Phase 2	-	The University of Texas MD Anderson Cancer Center	16 Jun 2021
Glioma	Phase 2	United States	Spectrum Pharmaceuticals, Inc.	23 Dec 2019
HER2-negative breast cancer	Phase 2	United States	Spectrum Pharmaceuticals, Inc.	23 Dec 2019
Microsatellite instability-high colorectal cancer	Phase 2	United States	Spectrum Pharmaceuticals, Inc.	23 Dec 2019
Triple Negative Breast Cancer	Phase 2	United States	Spectrum Pharmaceuticals, Inc.	23 Dec 2019
HER2 ex20ins mutation in non-small cell lung cancer	Phase 2	South Korea	Hanmi Pharmaceutical Co., Ltd.	13 Aug 2019
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 2	United States	Spectrum Pharmaceuticals, Inc.	11 Oct 2017
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 2	Belgium	Spectrum Pharmaceuticals, Inc.	11 Oct 2017
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 2	Canada	Spectrum Pharmaceuticals, Inc.	11 Oct 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03744715 (CTgov)	Phase 2	Breast Cancer \| Non-Small Cell Lung Cancer	7	Poziotinib (Poziotinib 6 mg)	whyypbpjst = zirqrvvwpx klirgagxrp (lhvacmpkko, ehhlobfsat - xdaoybvhbb) View more	-	28 Jul 2026
				Poziotinib (Poziotinib 8 mg)	whyypbpjst = tnpdcrdctn klirgagxrp (lhvacmpkko, sqasjsmrla - jwbhusrlev) View more
NCT04402008 (CTgov)	Phase 1/2	Non-Small Cell Lung Cancer	42	Poziotinib (Phase 1: Poziotinib 8 mg QD)	liqbyqrudz = bdbsnmxqgg fpsqkdvkje (augdwlbgga, etxorcbnxq - doubatdcqj) View more	-	25 Jun 2024
				Poziotinib (Phase 1: Poziotinib 12 mg QD)	liqbyqrudz = fjtbfrhnvp fpsqkdvkje (augdwlbgga, apmemawhdb - nkaciyqoci) View more
NCT04172597 (CTgov)	Phase 2	Microsatellite instability-high colorectal cancer \| Breast Cancer \| Triple Negative Breast Cancer ... View more	1	Poziotinib Hydrochloride+Loperamide (Cohort 1)	anmrvlubpi(ljdcvnaqad) = ywwjflzphe dzwcsbxkrc (hljuzcjghn, mgfufhzphj - vnpetqmvor) View more	-	13 Mar 2024
				Poziotinib Hydrochloride+Loperamide (Cohort 2)	anmrvlubpi(ljdcvnaqad) = kdhkkhbtxk dzwcsbxkrc (hljuzcjghn, dagxcpwacv - upwmdwrkes) View more
NCT03292250 (KCSG HN 15-16 TRIUMPH, Pubmed) Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck PIK3CA \| epidermal growth factor receptor/HER2 \| fibroblast growth factor receptor ... View more	203	Alpelisib	lhrkyyhxnp(mtgpuxskdr) = utttnevgxn tvpmblcivp (duphtsergi ) View more	Positive	10 Feb 2024
				Poziotinib	bpvleqgmfe(gztrksvjue) = iucptbijza nhwwnqqfpv (ulembmvktb ) View more
NCT03318939 (ZENITH20, ESMO2023)	Phase 2	Non-Small Cell Lung Cancer HER2	91	Poziotinib 16 mg QD	klnvmlzlke(mxpuwkqfnx) = ikaumnvznt hbxartsmuv (fvovhqpwet, [22 - 41]) View more	Positive	23 Oct 2023
				Poziotinib 8 mg BID	klnvmlzlke(mxpuwkqfnx) = rojllrxkls hbxartsmuv (fvovhqpwet )
NCT03318939 (ZENITH20, WCLC2023) Manual	Phase 2	Non-Small Cell Lung Cancer Third line HER2 exon 20 insertion	69	Poziotinib 16 mg	eowzurvqgi(kjtsmoshzt) = wcvwlwnudu dxpnoiluhq (zciiubmrez, 19.9 - 42.7) View more	Positive	11 Sep 2023
NCT03318939 (ZENITH20, ESMO2022)	Phase 2	HER2 ex20ins mutation in non-small cell lung cancer	170	Poziotinib 16 mg QD	sxguyampfc(otrkxhvisk) = qomcqjfwcb fskmmoxipd (zyhxcpopos ) View more	-	10 Sep 2022
				Poziotinib 8 mg BID	sxguyampfc(otrkxhvisk) = xlraynbsqi fskmmoxipd (zyhxcpopos ) View more
NCT03066206 (Pubmed)	Phase 2	Non-Small Cell Lung Cancer	50	Poziotinib	skrxloclij(seaqjrmjsv) = csgdxlnzrd kybenrkuuw (ceneontadt ) View more	Positive	11 Jul 2022
NCT02418689 (NOV120101-203, ESMO_BC2022) Manual	Phase 2	Metastatic human epidermal growth factor 2 positive carcinoma of breast HER2-positive	102	poziotinib	xcnhxojmdr(lkziotwjjh) = zrkqbftnmr nqkfymmeca (gtksyrkitd, 3.0 - 4.4) View more	Positive	04 May 2022
NCT03318939 (ZENITH20-4, ESMO_TAT2022)	Phase 2	HER2 ex20ins mutation in non-small cell lung cancer	70	Poziotinib 16 mg QD	ywbbhfnubl(lkslwprmoc) = fiqzaqsfts fqilzlbths (odclhblvab, 30% - 54%) View more	-	07 Mar 2022
				Poziotinib 8 mg BID	ywbbhfnubl(lkslwprmoc) = yazjtuiasd fqilzlbths (odclhblvab, 30% - 54%) View more