AiRuiKang (dalpiciclib) / Jiangsu Hengrui Pharma - LARVOL DELTA

Cyclin-Dependent 4/6 Kinase Inhibitors for Treatment of HER2-Positive Breast Cancer: 2026 Update. (PubMed, Cancers (Basel)) - "Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, abemaciclib, dalpiciclib) combined with endocrine therapy (ET) were a major advance in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) worldwide...However, clinical development of CDK4/6i in HER2+ MBC slowed, given the advent of highly effective tyrosine-kinase inhibitors (TKIs) (i.e., tucatinib) and antibody-drug conjugates (ADCs) (i.e., trastuzumab deruxtecan), which currently dominate the treatment armamentarium...Subsequently, the phase III PATINA trial (which included patients with 1L HR+HER2+ MBC, treated with palbociclib vs. placebo with maintenance ET+ H[P]) noted a striking PFS improvement of >15 months in the palbociclib arm, renewing interest in CDK4/6i-based treatments for HR+HER2+ MBC. Herein, we review the development of CDK4/6i in HER2+ BC, discussing current challenges and potential future..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-world efficacy and prognostic factors of CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer: a multicenter retrospective study from the Dongting Lake region of China. (PubMed, Transl Breast Cancer Res) - "The most commonly used CDK4/6i were abemaciclib (33.39%), dalpiciclib (28.98%), palbociclib (25.76%), and ribociclib (10.85%). CDK4/6i demonstrates favorable real-world efficacy in HR+/HER2- MBC patients in central China, particularly in the first-line setting. Several clinical factors may aid in treatment selection and risk stratification."

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

Study of Neoadjuvant Endocrine Therapy in HR Positive and HER2 Negative Premenopausal Breast Cancer Patients (clinicaltrials.gov) - P2/3 | N=119 | Completed | Sponsor: Tianjin Medical University Cancer Institute and Hospital | Recruiting ➔ Completed | Trial completion date: Sep 2026 ➔ Sep 2025

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

Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial (ESMO 2022) - P3 | "Clinical trial identification NCT03966898. Conclusions Adding dalp to letrozole/anastrozole significantly prolonged PFS in HR+/HER2- ABC, with manageable toxicities. Dalp is the 4 th CDK4/6 inhibitor showing survival benefit with letrozole or anastrozole in untreated HR+/HER2- ABC, or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib and abemaciclib."

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

An Open-Label, Randomized Controlled, Phase III Study of Dalpiciclib Plus Endocrine Therapy Versus Chemotherapy Followed by Endocrine Therapy in High-Risk HR+/HER2- Recurrent or Metastatic Breast Cancer (ChiCTR) - P4 | N=220 | Not yet recruiting | Sponsor: Cancer Hospital of Shandong First Medical University; Cancer Hospital of Shandong First Medical University

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

Dalpicilib combined with cetuximab in patients with HPV-negative, anti-PD-1-resistant recurrent or metastatic head and neck squamous cell carcinoma: A phase II trial. (PubMed, Nat Commun) - P2 | "No grade 4 or 5 TRAEs were observed. Dalpiciclib combined with cetuximab was well-tolerated and showed promising efficacy in patients with anti-PD-1-resistant, HPV-negative recurrent and/or metastatic HNSCC."

Journal • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

The synergistic tumor suppressor effect of CDK4/6 inhibitors and BRD4 inhibitors in acute myeloid leukemia. (PubMed, Leuk Res Rep) - "5. SHR6390 and OTX015 Synergistically Inhibit the Growth of AML Xenografts In Vivo."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BRD4

Dalpiciclib in HR+/HER2- ABC (clinicaltrials.gov) - P=N/A | N=103 | Recruiting | Sponsor: RenJi Hospital | Trial primary completion date: Dec 2025 ➔ Jan 2027

Real-world evidence • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of Dalpiciclib in the treatment of hormone receptor-positive advanced breast cancer a multicenter observational real-world study (ChiCTR) - P=N/A | N=500 | Recruiting | Sponsor: Harbin Medical University Affiliated Cancer Hospital; Harbin Medical University Affiliated Cancer Hospital

New trial • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • PGR

A Study to Evluate Efficacy and Safety of HRS-8080 Combined With Dalpiciclib in Patients With Advanced or Metastatic Breast Cancer Resistant to Adjuvant Endocrine Therapy. (clinicaltrials.gov) - P3 | N=912 | Not yet recruiting | Sponsor: Shandong Suncadia Medicine Co., Ltd.

New P3 trial • Breast Cancer • Oncology • Solid Tumor

DNADalHR: ctDNA-Guided De-Escalation of Adjuvant Chemotherapy With Dalpiciclib in HR-Positive/HER2-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=393 | Recruiting | Sponsor: Peking University People's Hospital | Not yet recruiting ➔ Recruiting

Circulating tumor DNA • Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Dalpiciclib versus placebo in combination with letrozole or anastrozole as first-line treatment for women with HR+/HER2- advanced breast cancer: prespecified final analysis of progression-free survival of the phase 3 DAWNA-2 trial. (SABCS 2024) - P3 | "The addition of dalpiciclib to letrozole or anastrozole continues to demonstrate PFS benefits with no new safety signals identified after prolonged follow-up, further supporting this regimen as an alternative option in the current treatment landscape for patients with HR+/HER2- advanced breast cancer, regardless of menopausal status."

Clinical • Combination therapy • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Dalpiciclib (Dalp) plus endocrine therapy (ET) as adjuvant treatment for HR+/HER2– early breast cancer (BC): The randomized, phase 3, DAWNA-A trial. (ASCO 2025) - P3 | "Patients (pts) were randomized (1:1) to receive oral Dalp (125 mg QD; 3-wk on/1-wk off, for 2 y) + ET (letrozole 2.5 mg/anastrozole 1 mg/tamoxifen 10 mg/toremifene 60 mg QD, for 5 y) or placebo + ET. Addition of Dalp to ET as adjuvant treatment significantly improved iDFS, with a tolerable safety profile. These data support the use of Dalp for treating HR+/HER2- early BC. Efficacy outcomes.*Kaplan–Meier method."

Clinical • 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

Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Our findings suggest that dalpiciclib plus letrozole or anastrozole could be a novel standard first-line treatment for patients with hormone receptor-positive, HER2-negative advanced breast cancer, and is an alternative option to the current treatment landscape."

Journal • Metastases • P3 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • HER-2

Efficacy and safety of dalpiciclib, exemestane, and goserelin as neoadjuvant therapy in premenopausal HR-positive, HER2-negative breast cancer patients: A phase II clinical trial (ESMO 2024) - P2/3 | "Participants initially received two cycles of TAC (docetaxel, doxorubicin, and cyclophosphamide). Preliminary results advocate for the use of dalpiciclib, exemestane, and goserelin as an effective alternative to continued chemotherapy in premenopausal HR-positive, HER2-negative BC patients unresponsive to initial neoadjuvant chemotherapy. This strategy offers notable treatment benefits, diminishes adverse events, and enhances patient quality of life. Further enrollment up to 43 participants will continue based on these findings."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical Study of HRS-8080 in Combination With Dalpiciclib Isethionate Tablets in Patients With Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P1/2 | N=146 | Recruiting | Sponsor: Shandong Suncadia Medicine Co., Ltd. | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Randomised, Open-label, Multicentre Phase III Clinical Study to Evaluate the Efficacy and Safety of JS105 Combined With Dalpiciclib and Fulvestrant Compared With Dalpiciclib and Fulvestrant in Patients With PIK3CA-mutated, HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer. (clinicaltrials.gov) - P3 | N=312 | Recruiting | Sponsor: Risen (Suzhou) Pharma Tech Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

SHR-A1811 Plus Pertuzumab as Neoadjuvant Therapy for Early or Locally Advanced HR-Positive HER2-Positive Breast Cancer: A Prospective, Open-Label, Phase II Study (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Tianjin Medical University Cancer Institute and Hospital

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Case Report: Solitary scalp metastasis after surgery for invasive ductal carcinoma of the breast. (PubMed, Front Oncol) - "The patient was started on systemic therapy with fulvestrant plus dalpiciclib, and after four cycles, she achieved marked regression of the scalp lesion along with resolution of periorbital edema. Consequently, the patient received localized radiotherapy to these sites while continuing the original treatment protocol. This case highlights the diagnostic challenges of atypical scalp metastases in breast cancer and underscores the importance of early detection and prompt initiation of comprehensive treatment."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Precision neoadjuvant treatment with Artificial Intelligence assisted subtyping in HR+/HER2- breast cancer: a randomized, open-label, phase 2 trial FASCINATE-N (SABCS 2025) - P2 | "Precision treatments included six cycles of dalpicilib (CDK4/6 inhibitor) plus endocrine therapy every 4 weeks for endocrine-based group and six cycles of targeted therapy (SHR-1316 [PD-L1 inhibitor] for SNF2, fuzuloparib [PARP1 inhibitor] for SNF3 and apatinib [VEGFR inhibitor] for SNF4) plus nab-paclitaxel and carboplatin every 4 weeks for targeted-based group. NET plus CDK4/6 inhibitor was verified to replace chemotherapy with better tolerance in the endocrine-base group while precision therapy was proved promising clinical activity and manageable safety profile in the targeted-based group. (ClinicalTrials.gov: NCT05582499)."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • SMARCA2

Different Doses of Dalpicicl Combined With Letrozole in the First-line Treatment of HR-positive, HER2-negative Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: wanghaibo

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Dalpiciclib plus endocrine therapy as adjuvant treatment for HR+/HER2- early breast cancer: updated results from the phase 3, DAWNA-A trial (SABCS 2025) - P3 | "Methods Women aged 18-75 yrs, with HR+/HER2-, node-positive, stage II-III BC were randomized (1:1) to receive Dalp (125 mg QD, 3-wk on/1-wk off, for 2 yrs) or placebo, both with ET (letrozole 2.5 mg, anastrozole 1 mg, or toremifene 60 mg QD, or tamoxifen 10 mg BID, for ≥5 yrs). Conclusions Addition of Dalp to adjuvant ET contiuned to show clinically meaningful improvement in IDFS within and beyond the 2-yr treatment period, with a manageable safety profile. These findings support the adjuvant use of Dalp for HR+/HER2- EBC."

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

Neoadjuvant Dalpiciclib Plus Letrozole Versus Standard Chemotherapy in High-Risk HR+/HER2- Negative Breast Cancer (DARLING-02): A Randomized Phase II Trial (SABCS 2025) - P2 | "The control arm received epirubicin 100 mg/m² plus cyclophosphamide 500 mg/m² intravenously on day 1 every 3 weeks for 4 cycles, followed by docetaxel 100 mg/m² intravenously on day 1 every 3 weeks for 4 cycles. These findings support dalpiciclib plus letrozole as a promising neoadjuvant option for patients with high-risk HR+/HER2- early breast cancer and warrant confirmation in phase III trials."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Cycline Dipendent Kinase inhibitors 4/6 and endocrine therapy in the first line of treatment for HR+Her2- advanced breast cancer: a meta-analysis of the published real-world studies (SABCS 2025) - "A systematic literature search was performed using PubMed with the terms: "breast cancer," "real world," "palbociclib," "abemaciclib," "ribociclib" "dalpiciclib". This analysis did not reveal significant differences in 2-year rwPFS, the primary outcome in most real-world studies, among the CDK4/6 inhibitors. Any observed differences between R and P should be interpreted with consideration for the patient characteristics within the studies analysed. Further adjustment of the analysis using multiple variables is planned to assess inter-trial differences and mitigate bias inherent in real-world settings."

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