AiRuiNi (pyrotinib) / Jiangsu Hengrui Pharma, HLB Bio Group - LARVOL DELTA

Efficacy and Safety Ranking of HER2-Targeted TKIs in Advanced Breast Cancer: A Bayesian Network Meta-Analysis. (PubMed, Clin Med Insights Oncol) - "Tucatinib combined with trastuzumab and capecitabine (Tucatinib_T_C) demonstrated the highest probability of favorable OS ranking. Regarding safety, pyrotinib combined with trastuzumab and capecitabine (Pyrotinib_T_C) was associated with the highest incidence of serious adverse events, diarrhea, and hand-foot syndrome, whereas Pyrotinib_C showed the highest incidence of anemia and lapatinib plus capecitabine (Lapatinib_C) demonstrated the highest incidence of rash...However, pyrotinib-containing regimens were associated with a higher risk of treatment-related toxicities. These findings highlight the importance of balancing efficacy and safety when selecting HER2-targeted TKI therapies and support individualized treatment strategies for patients with HER2-positive advanced breast cancer."

Journal • Retrospective data • Breast Cancer • Dermatology • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Inetetamab Combined with Pyrotinib for HER2-Positive Advanced Breast Cancer: A Multicenter Real-World Retrospective Study (ESMO 2026) - No abstract available

Metastases • Real-world • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Metformin exhibits a synergistic effect with pyrotinib by inducing ferroptosis in HER2-positive cancers through the Keap1/Nrf2 pathway. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "In vivo experiments using the SKOV-3 xenograft model show that the combination therapy significantly enhances antitumor efficacy compared to monotherapy, without causing noticeable toxicity. These results suggest that combining pyrotinib with metformin may provide an effective therapeutic strategy for HER2-positive cancers."

Journal • Diabetes • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • HER-2

Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase 2 trial. (PubMed, Ann Oncol) - P2 | "This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. SHR-A1811 showed robust activity, with a tolerable safety profile. (ClinicalTrials.gov, NCT05582499)."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial. (PubMed, Nat Med) - "The phase 2 trial CU cohort (n = 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n = 8) had no responses to physician's therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively."

Journal • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Neoadjuvant Trastuzumab and Pyrotinib for Locally Advanced HER2-Positive Breast Cancer (NeoATP): Primary Analysis of a Phase II Study. (PubMed, Clin Cancer Res) - "The addition of pyrotinib to trastuzumab plus chemotherapy is an efficacious and safe regimen for patients with HER2-positive locally advanced breast cancer in the neoadjuvant setting. The randomized controlled clinical trial is warranted to validate our results."

Clinical • Journal • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • HER-2 • PIK3CA

A Study Evaluating the Safety and Efficacy of Pyrotinib Dose Escalation Plus Loperamide Prophylaxis in First-Line Treatment of Advanced HER2-Positive Breast Cancer (ESMO 2026) - No abstract available

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

Dual HER2 Targeted Therapy With Pyrotinib and Trastuzumab in Refractory HER2 Positive Metastatic Colorectal Cancer: A Result From HER2-FUSCC-G Study. (PubMed, Clin Colorectal Cancer) - P2 | "Trastuzumab in combination with pyrotinib demonstrated encouraging antitumor activity that translated to prolonged survival benefit in HER2 positive refractory or mCRC patients who are RAS wild-type with acceptable tolerance."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • BRAF

Pyrotinib for HER2-Positive Advanced Breast Cancer Previously Treated With Trastuzumab and Pertuzumab (clinicaltrials.gov) - P=N/A | N=200 | Active, not recruiting | Sponsor: Beijing 302 Hospital

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

Neoadjuvant ARX788 plus pyrotinib versus trastuzumab, pertuzumab, docetaxel and carboplatin for HER2-positive breast cancer: a randomised phase 2b trial. (PubMed, Nat Commun) - P2/3 | "Interstitial lung disease (ILD)/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. These findings offer clinical insights into the potential of dual HER2-targeted blockade with an ADC and TKI as an optional neoadjuvant strategy for patients with early or locally advanced HER2-positive breast cancer."

Clinical • Journal • P2b data • Anorexia • Breast Cancer • Fatigue • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Liver Failure • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Efficacy and safety of brain radiotherapy combined with antibody-drug conjugates in patients with HER2-positive breast cancer brain metastases. (PubMed, Front Oncol) - "Most patients had prior pyrotinib treatment. In this unadjusted retrospective cohort, patients receiving radiotherapy combined with T-DXd exhibited longer univariate survival outcomes compared with those treated with T-DM1. However, these univariate observational results are preliminary and require prospective multicenter validation with multivariate adjustment."

Journal • Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Leukopenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • HER-2

Early Clinical Outcomes of VRN101099 in ERBB2-Mutated Advanced Non-Small Cell Lung Cancer: A Case Series From a Phase 1A Study (IASLC-WCLC 2026) - P1 | "Trastuzumab deruxtecan (T-DXd) has shown activity in HER2-mutant NSCLC but with limited durability; poziotinib and pyrotinib provide incomplete mutational coverage with dose-limiting toxicities; and current agents exhibit poor CNS penetration...All had progressed on prior HER2-targeted therapies including T-DXd (n=3) and tucatinib/trastuzumab (n=1)...Conclusions : In this Phase 1a case series, VRN101099 demonstrated preliminary antitumor activity across multiple ERBB2 mutation types and tumor histologies, including patients with CNS disease and those refractory to prior HER2-targeted therapies. These findings support the continued evaluation in planned dose-expansion cohorts to further characterize the efficacy and safety of VRN101099 in ERBB2-mutant malignancies."

Clinical • Clinical data • Metastases • P1 data • Breast Cancer • CNS Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • HER-2 • KRAS • PIK3CA • TP53

Dalpiciclib plus Pyrotinib-Based Chemotherapy-Free Regimens as first line treatment in Trastuzumab-Sensitive, HER2-Positive Metastatic Breast Cancer (DAP-HER-02): A Dual-Cohort, Phase II Study (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway."

Journal • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2

Neoadjuvant Chemotherapy plus Pyrotinib and Trastuzumab for HER2-positive Breast Cancer: A Prospective, Single-arm, Multi-center Study (NEOTORCH-BREAST05) (ESMO 2026) - No abstract available

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

Updated overall survival (OS) results from the phase 3 PHOEBE trial of pyrotinib versus lapatinib in combination with capecitabine in patients with HER2-positive metastatic breast cancer (SABCS 2021) - P3 | "With extended follow-up, pyrotinib plus capecitabine demonstrated statistically significant OS improvement compared with lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy. This updated analysis of overall survival in the PHOEBE trial reaffirmed pyrotinib plus capecitabine as an established treatment option in this patient population. Data are median (95% CI)."

Clinical • Combination therapy • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • EGFR • ER • ERBB4 • HER-2 • PGR

Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer (mBC): prespecified final analysis of progression-free survival (PFS) of the phase 3 PHILA trial. (SABCS 2024) - P3 | "After an extended follow-up period, the updated analysis demonstrates that PyroHT provides sustained longer PFS compared to HT, which translates into longer OS for PyroHT than HT in the first-line treatment of HER2-positive mBC. The safety profile of PyroHT remained manageable throughout the extended treatment duration. This updated analysis further reinforces PyroHT as a well-established and efficacious therapeutic strategy for this patient population."

Clinical • Combination therapy • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • ERBB4 • HER-2

First-line pyrotinib plus apatinib in advanced non-small cell lung cancer harboring HER2 mutations or amplification: a phase II trial. (PubMed, Lung Cancer) - "Pyrotinib combined with apatinib demonstrated promising first-line activity, rapid responses, and manageable toxicity in advanced HER2-altered NSCLC, supporting its potential as an accessible chemotherapy-sparing therapy, particularly in resource-constrained settings."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Pyrotinib combined with metronomic etoposide in heavily pretreated HER2-positive metastatic breast cancer: a single-arm, phase II study. (PubMed, BMC Cancer) - P2 | "The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity."

Journal • Metastases • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2

Safety and preliminary efficacy of GQ1001, a next generation HER2-targeting ADC, combined with pyrotinib in pretreated patients with HER2-positive metastatic breast cancer: A phase 1b clinical trial. (ASCO 2024) - P1, P1/2 | "3% of the patients (5/15) had been treated with pertuzumab. GQ1001 in combination with pyrotinib demonstrated manageable safety profile and promising preliminary antitumor activity among pretreated patients with HER2-positive metastatic breast cancer. [1] HUANG L, et al. Cancer Research, 2023, 83(7_Supplement): 2702-."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Dermatology • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Oncology • Solid Tumor • Thrombocytopenia • Urticaria • HER-2

Neoadjuvant Inetetamab and Pyrotinib and Nab-paclitaxel for HER2+Breast Cancer (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Xijing Hospital | Not yet recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Neoadjuvant Pyrotinib-to-pertuzumab in HER2+ eBC (clinicaltrials.gov) - P3 | N=220 | Recruiting | Sponsor: Shanghai Jiao Tong University School of Medicine

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab rezetecan versus pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer (HORIZON-Breast01): interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Trastuzumab rezetecan improved progression-free survival versus pyrotinib plus capecitabine and showed a distinct safety profile in patients with HER2-positive breast cancer, presenting as a potential new treatment option."

Journal • P3 data • P3 data: top line • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • HER-2

HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-positive Early Breast Cancer: a Prospective, Randomized, Open-label, Phase 2 Trial. (SABCS 2024) - P2 | "Patients were randomly assigned (1:1:1) to receive nab-paclitaxel (100mg/m2 i.v. day 1, day 8, and day 21 in a 28-day per cycle) combined with carboplatin(AUC 1.5 i.v. day 1, day 8, and day 21 in a 28-day per cycle), trastuzumab(initial dose 8mg/kg, subsequent dose 6mg/kg i.v. every 3weeks), and pertuzumab (initial dose 840mg, subsequent dose 420mg i.v. every 3weeks) for 6 cycles (PCbHP), SHR-A1811 monotherapy (4.8mg/kg i.v. day 1 every 3weeks) for 8 cycles, or SHRA1811 with pyrotinib (240mg orally once a day daily) for 8 cycles. Interpretation This is the first study to report the efficacy of third generation HER2-directed ADC in the neoadjuvant setting of HER2 positive breast cancer. SHR-A1811 exhibited promising antitumor activity and acceptable tolerability, with monotherapy pCR rate up to 63%."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor