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

Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study (ESMO 2025) - P3 | "Results A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). Conclusions A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • 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

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

Triple HER2 Blockade With Trastuzumab, Pertuzumab, and Pyrotinib Versus Dual HER2 Blockade in the Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Randomized, Phase II Study. (PubMed, MedComm (2020)) - "Patients with stage II-III HER2-positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab-paclitaxel for 12 weeks. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea."

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

Safety Study of the Combination Regimen Based on HuA21 Monoclonal Antibody for the Treatment of Advanced HER2-overexpressing Solid Tumors (ChiCTR) - P=N/A | N=90 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Anhui Medical University

New trial • Breast Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

CD24 overexpression confers resistance to Pyrotinib through inhibiting autophagy in patients with HER2-positive breast cancer. (PubMed, Int J Biol Macromol) - "Furthermore, CD24 knockdown reduced its expression level by promoting the ubiquitination modification of epidermal growth factor receptor (EGFR), and significantly inhibited its downstream AKT/mTOR signaling pathway. By interacting with EGFR and modulating the mTOR pathway, CD24 acted as a critical regulator of autophagic cell death, thereby enhancing the sensitivity of HER2+ BC cells and reversing Pyrotinib resistance."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD24 • 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

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

Efficacy and Safety of Paclitaxel Oral Solution in Combination with Trastuzumab for Subcutaneous Injection and Pyrotinib as First-line Treatment for HER2-positive Recurrent/Metastatic Breast Cancer (ChiCTR) - P=N/A | N=43 | Not yet recruiting | Sponsor: Beijing Cancer Hospital; Beijing Cancer Hospital

New trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

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

Radiation therapy combined with tyrosine kinase inhibitors in 826 patients with HER2-positive breast cancer brain metastases: a systematic review and network meta-analysis. (PubMed, Neurosurg Rev) - "Bayesian network meta-analysis (NMA) was conducted to integrate direct and indirect comparisons, addressing the lack of head-to-head trials. Eleven studies (2 RCTs, 9 retrospective; 826 patients) evaluated four treatment strategies: pyrotinib + RT, pyrotinib alone, RT alone, and lapatinib + RT. In contrast, lapatinib + RT appeared to offer limited benefit and a higher risk of SAEs. Further randomized controlled trials are needed to validate these findings."

Clinical • Journal • Retrospective data • Review • 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

Efficacy and safety of pyrotinib-based regimens in patients with HER2-positive stage III/IV breast cancer: a real-world retrospective study in China. (PubMed, PeerJ) - "A subgroups comparison found that significant differences were observed in patients who had not used lapatinib (P = 0.016), had a number of metastatic sites ≤ 2 (P = 0.011), were intolerant to trastuzumab (P = 0.004), and were on first-line pyrotinib treatment (P = 0.036), with these patients having median progression-free survival lengths of 13.0 months, 15.9 months, 23.5 months, and 23.5 months, respectively. In addition, a rare positive fecal occult blood profile (5.4%) was observed. Pyrotinib-based regimens have shown satisfactory clinical efficacy in HER2-positive stage III/IV BC patients, and pyrotinib is well tolerated with manageable adverse events."

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

Exploration of Targeted Therapy Regimens for Triple-Positive Breast CancerExploration of Targeted Therapy Regimens for Triple-Positive Breast Cancer (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

New trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor 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

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 Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab in HER2+ Breast Cancer (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Shanghai Jiao Tong University School of Medicine

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • 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

Updated efficacy of lenvatinib (LEN) + pembrolizumab (PEMBRO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in the CLEAR study (ESMO 2022) - P3 | "Editorial acknowledgement Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. A large proportion of pts treated with LEN + PEMBRO completed 2 yrs of PEMBRO and continued with LEN monotherapy with ongoing clinical benefit. The results further support LEN + PEMBRO as a standard of care in 1L aRCC."

Clinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Additional analyses of MOUNTAINEER: A phase II study of tucatinib and trastuzumab for HER2-positive mCRC (ESMO 2022) - P2 | "Editorial acknowledgement Under guidance of the authors, assistance in medical writing was provided by Irene Park, PhD, of Seagen Inc. Disease stabilization was observed in most pts on TUC monotherapy; radiographic responses increased slightly after Tras addition. Monotherapy, crossover, and response data from the primary analysis show that concurrent initiation of dual HER2 blockade with TUC + Tras achieves optimal clinical benefit."

Late-breaking abstract • P2 data • Colorectal Cancer • Oncology • HER-2

Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer (clinicaltrials.gov) - P3 | N=160 | Active, not recruiting | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

SHR-A1811 versus pyrotinib plus capecitabine in human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (BC): A multicenter, open-label, randomized, phase III study (HORIZON-Breast01) (ESMO 2025) - P3 | "Methods Taxane- and trastuzumab-pretreated patients (pts) with HER2+ advanced/metastatic BC were randomized (1:1) to receive intravenous SHR-A1811 or oral pyrotinib plus capecitabine...Results As of Jun 30, 2025, 287 pts were randomized (SHR-A1811, n=142; pyrotinib plus capecitabine, n=145; IHC 3+: 76.1% vs. 71.7%; HR+: 47.9% vs. 47.6%; median lines of prior systemic treatments: 1 vs.1; prior pertuzumab: 71.8% vs. 72.4%), with median follow-up of 15.9 months (95% CI 14.6–17.1) for SHR-A1811, and 15.3 months (95% CI 14.3–16.6) for pyrotinib plus capecitabine...b 1-sided c. assessed in treated pts. Conclusions SHR-A1811 exhibited significant PFS benefit and strong trend in OS benefit versus pyrotinib plus capecitabine in the second-line therapy in HER2+ advanced/metastatic BC, with favorable safety profile of low ILD occurrence."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. (PubMed, Front Oncol) - P1/2 | "The planned dose-expansion phase II study is ongoing. ClinicalTrials.gov, identifier NCT03772353."

Journal • P1 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukopenia • Mucositis • Neutropenia • Oncology • Solid Tumor • Stomatitis • HER-2