Nerlynx (neratinib) / Boryung Group, Puma, Specialised Therap, Knight Therap, Pierre Fabre, Fosun Pharma, Convalife, BIXINK Therapeutics, Er-Kim Pharma, Shenzhen Kexing Pharma, Shanghai Henlius Biotech - LARVOL DELTA

Neratinib, a multi-targeted receptor tyrosine kinase inhibitor in advanced Non-small-cell Lung Cancer with exon 18 mutations EGFR mutations (ESMO 2026) - No abstract available

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

THUNDER: T-DXd With or Without Neratinib for HER2 Positive Breast Cancer With Brain Metastasis (clinicaltrials.gov) - P2 | N=202 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2029 ➔ Nov 2031 | Trial primary completion date: Nov 2027 ➔ Aug 2029

Enrollment open • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Unveiling Disulfidptosis and Cuproptosis Vulnerabilities in Pterygium: A Transcriptomic Analysis and In-Silico Drug Repurposing Strategy. (PubMed, Genes (Basel)) - "Pterygium is associated with coordinated transcriptional alterations involving disulfidptosis- and cuproptosis-related gene networks, suggesting potential structural and metabolic vulnerabilities. In-silico drug repurposing identified several pharmacological candidates whose transcriptional effects oppose the observed disease-associated signature. These findings provide a rationale for further experimental investigation of these pathways and candidate compounds in pterygium."

Journal • Ophthalmology • SLC31A1

Multi-omics Reveals Divergent Endothelial Molecular Responses to New and Old World Hantaviruses. (PubMed, bioRxiv) - "Additionally, ANDV induced heightened activity of ERBB-family kinases, whose chemical inhibition by neratinib and afatinib reduced viral replication. Together, these data define species-specific responses in endothelial cells, identify druggable host targets, and reveal mechanisms with relevance to divergent vascular leakage symptomology."

Journal • Infectious Disease

Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial (ESMO-BC 2025) - P1 | "We report the final analysis of a phase I trial of zani + chemo in pts with HER2-expressing mBC. Part 3 of the phase I trial (NCT02892123) evaluated zani + chemo (paclitaxel [pac], capecitabine [cap] or vinorelbine [vin]) or zani + cap + tucatinib (tuc) in pts with HER2-expressing mBC...Prior (>5% of pts) anti-HER2 therapies included trastuzumab (93%), T-DM1 (91%), pertuzumab (80%), lapatinib (24%), T-DXd (9%), tuc (9%), and neratinib (7%)... Zani + chemo had a manageable safety profile and good tolerability with promising antitumour activity and durable responses in heavily pretreated pts with HER2-expressing mBC. Among pts with HER2+ mBC with prior HER2-targeted regimens, adding zani to chemo showed encouraging PFS."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Translational Breast Cancer Research Consortium Trial 022: Neratinib and Trastuzumab-Emtansine for HER2+ breast cancer brain metastases (BCBM) (SABCS 2022) - "We previously reported that neratinib monotherapy is associated with a volumetric central nervous system objective response rate (CNS ORR) of 8%, whereas the combination of neratinib and capecitabine resulted in a volumetric CNS ORR of 49% (in lapatinib-naïve pts)...Across Cohorts 4A-4C, the median number of prior lines of chemotherapy prior to enrollment was 2 (range 1-10); 25% received prior lapatinib and no patients received prior tucatinib... Intracranial activity was observed for the combination of neratinib plus T-DM1 across all three enrolled cohorts, including those with prior T-DM1 exposure, suggesting synergistic effects of this treatment combination. Our data provide additional evidence for consideration of neratinib- based combinations in pts with HER2+ BCBM."

Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations. (PubMed, ESMO Open) - "Pharmacokinetic data indicated reduced neratinib clearance possibly due to CYP3A4 pathway saturation by everolimus. Combination therapy with neratinib and everolimus has a tolerable safety profile and clinical activity in ErbB-altered patients. ErbB family receptors and the PI3K pathway are commonly implicated in oncogenesis. This clinical study of neratinib and everolimus demonstrated favorable clinical activity and tolerability."

Journal • P1 data • Acute Kidney Injury • Breast Cancer • Endometrial Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Mucositis • Nephrology • Oncology • Renal Disease • Solid Tumor • CYP3A4 • HER-2

Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis. (PubMed, Front Pharmacol) - "This study addresses the safety profiles and molecular mechanisms of trastuzumab monotherapy and its combination with lapatinib, neratinib, and tucatinib for treating HER2-positive tumors. This study establishes a novel framework for drug safety evaluation and provides a theoretical rationale for optimizing therapeutic strategies in HER2-positive tumors. These findings highlight the potential advantages of combination therapies regarding AE latency and elucidate the critical role of HSP90AA1."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDC37 • HER-2 • HSP90AA1

Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Ruth O'Regan | Trial completion date: Jul 2027 ➔ Dec 2027 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022. (PubMed, Ann Oncol) - "We observed Intracranial activity for neratinib plus T-DM1, including those with prior T-DM1 exposure, suggesting synergistic effects with neratinib. Our data provide additional evidence for neratinib-based combinations in patients with HER2-positive BCBM, even those who are heavily pre-treated."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Neratinib and Fam-Trastuzumab Deruxtecan in Advanced Gastro-esophageal Cancer Patients (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial completion date: Jun 2027 ➔ Jun 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers. (PubMed, Nat Commun) - P2 | "Diarrhoea is the most common adverse event, with any-grade diarrhoea in 14 patients (56%). Although neratinib demonstrates antitumour activity in patients with refractory BTC harbouring HER2 mutations, the primary endpoint was not met and combinations may be explored."

Journal • Metastases • Ampulla of Vater Carcinoma • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • CDKN2A • HER-2 • TP53

Neoadjuvant targeted therapy in early resectable HER2-mutant lobular breast cancer. (ASCO 2024) - P2 | "Neratinib is a HER2 tyrosine kinase inhibitor (TKI) currently FDA-approved for adjuvant treatment of HER2-amplified (HER2+) early-stage breast cancer...We posit results from this study may generate a clear signal of clinical activity leading to a randomized phase III trial aimed at incorporating HER2-directed therapies as a treatment for operable, early stage ILC. This signal may also suggest for the first time the added value of NGS in patients with newly diagnosed HR+ breast cancer."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDH1 • HER-2

An Open-label, Two-Cohort, Phase II Study Evaluating Efficacy and Safety of NLX + NVB-Based Regimens in HER2-Positive MBC (ChiCTR) - P4 | N=321 | Not yet recruiting | Sponsor: Shanghai GoBroad Cancer Hospital; Shanghai GoBroad Cancer Hospital

New P4 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Electrochemical Behavior of Neratinib at a Boron-Doped Diamond Electrode: Role of Tween 20 in Interfacial Signal Enhancement. (PubMed, ACS Omega) - "The limits of detection and quantification were 5.09 nM (2.84 ng mL-1) and 15.16 nM (8.44 ng mL-1), respectively. Overall, the outcomes demonstrate that the analytical enhancement of NER at BDDE originates from surfactant-mediated, analyte-specific interfacial impacts and ensure a mechanistic basis for its sensitive voltammetric determination."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

The phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2 mutated, non-amplified metastatic breast cancer. (PubMed, Clin Cancer Res) - "Neratinib and fulvestrant is active for ER+/HER2 MBC. Our data supports further evaluation of dual HER2 blockade for the treatment of HER2 MBC."

Combination therapy • Journal • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Eur J Cancer) - P3 | "Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. (PubMed, Ann Oncol) - "The benefit of N+F+T for HR+ HER2-mutant MBC after progression on CDK4/6 inhibitors is clinically meaningful and, based on this study, N+F+T has been included in National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy."

Biomarker • Journal • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • PIK3CA

Longitudinal evaluation of health-related quality of life in Chinese patients with early-stage HER2-positive breast cancer undergoing neratinib extended adjuvant therapy: a real-world prospective cohort study. (PubMed, Front Oncol) - "This single-center, prospective observational study included 31 female patients diagnosed with stage I-III HER2-positive breast cancer who initiated neratinib therapy following the completion of trastuzumab-based adjuvant treatment between October 2022 and January 2024. Neratinib-associated HRQoL impairment is transient, with initial declines primarily due to diarrhea, which typically resolves within 3-6 months of treatment. With the implementation of appropriate supportive measures, such as loperamide prophylaxis and dose modifications, the majority of patients experience sustained HRQoL recovery, and even improvement, over a 12-month period."

HEOR • Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Concurrent human epidermal growth factor receptor 2-positive breast cancer with axillary nodal metastasis in a patient with pituitary prolactinoma: a case report. (PubMed, AME Case Rep) - "Adhering to a multidisciplinary plan while maintaining her cabergoline regimen uninterrupted, she received adjuvant chemotherapy, dual anti-HER2 blockade (trastuzumab and pertuzumab), and radiotherapy. She declined extended adjuvant neratinib due to gastrointestinal toxicity concerns...Furthermore, the paradoxical early lymphatic dissemination of a sub-centimeter primary tumor under physiological PRL levels suggests profound local crosstalk between HER2 and PRL receptor (PRLR) signaling. This necessitates vigilant management of even small, highly proliferative lesions in patients with concurrent endocrine comorbidities."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Pituitary Gland Carcinoma • Solid Tumor • HER-2 • PRL • PRLR

Mechanisms of TKI-induced hepatotoxicity: Linking oxidative stress to cellular senescence and macrophage polarization | Poster Board #1681 (ACS-Fall 2026) - "Lapatinib and neratinib are small-molecule tyrosine kinase inhibitors widely used in the treatment of HER2-positive metastatic breast cancer. Overall, this study highlights a novel mechanism of tyrosine kinase inhibitor-induced hepatotoxicity driven by senescence-mediated immune modulation. Integrating senescence biomarkers with macrophage polarization analysis provides a comprehensive framework for evaluating drug-induced liver injury, offering critical insights for identifying predictive biomarkers and therapeutic targets to mitigate the adverse effects of targeted cancer therapies."

Oxidative stress • Breast Cancer • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immune Modulation • Immunology • Liver Failure • Metabolic Disorders • Solid Tumor • CYP3A4 • HER-2

Neuroepithelial reprogramming and ERBB vulnerability in canine acanthomatous ameloblastoma. (PubMed, Mol Ther Oncol) - "A kinase inhibitor screen independently identified ERBB4 as a candidate therapeutic vulnerability, and pharmacologic inhibition with neratinib was effective. Together, these findings reveal a previously unrecognized neuroepithelial cell state that defines CAA, distinguishes it from COSCC, and reveals unique diagnostic and therapeutic signaling dependencies. Given the molecular/histopathologic parallels between CAA and human ameloblastoma, these data further position CAA as a naturally occurring comparative model for studying ameloblastoma therapeutic vulnerabilities."

Journal • Oncology • Oral Cancer • Skin Cancer • Squamous Cell Carcinoma • ERBB4 • KRAS

Puma Biotechnology Reports Second Quarter 2026 Financial Results (Businesswire) - "Product revenue, net consists entirely of revenue from sales of NERLYNX, Puma’s first commercial product. Product revenue, net in the second quarter of 2026 was $53.6 million, compared to product revenue, net of $49.2 million in the second quarter of 2025."

Sales • HER2 Positive Breast Cancer

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases. (PubMed, Breast) - P2 | "This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Targeting Oncogenic HER2 Mutations by Neratinib-induced HER2 Ubiquitination and Degradation in Breast Cancer. (PubMed, Curr Cancer Drug Targets) - "Drug-resistant HER2 mutations can be suppressed by neratinib-induced endocytic degradation, resulting in effective suppression of cancer cell growth."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • HER-2