AiRuiKang (dalpiciclib) / Jiangsu Hengrui Pharma - LARVOL DELTA

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 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

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

Dalpiciclib Plus Pyrotinib Plus Letrozole for Patients with Estrogen Receptor-Positive and HER2-Positive Metastatic Breast Cancer (DAPLET) (SABCS 2025) - P2 | "Standard metastatic regimens combining trastuzumab-based HER2-targeted therapy with chemotherapy show limited efficacy in this subtype. This chemotherapy-free, trigeminy-targeted regimen demonstrated promising antitumor activity and manageable toxicity in first or second line HER2+ER+ metastatic breast cancer. The data supported this regimen as a potential alternative to standard chemotherapy-based approaches in this subtype. Efficacy of this regimen needs to be further evaluated in Simon stage II."

Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Neoadjuvant pyrotinib, trastuzumab, dalpiciclib, and exemestane in triple-positive breast cancer: a multicenter phase II trial (SABCS 2025) - "The NA-PHER2 study demonstrated the potential benefit of a chemotherapy-free regimen, trastuzumab, pertuzumab, palbociclib, and fulvestrant, in TPBC...In the phase II MUKDEN 01 trial, pyrotinib combined with dalpiciclib and letrozole showed promise in TPBC, though efficacy remains suboptimal... This chemotherapy-free, quadruple-targeted neoadjuvant regimen demonstrated promising activity and manageable toxicity in early-stage TPBC. These data support further evaluation of this regimen as a potential alternative to standard chemotherapy-based neoadjuvant approaches in TPBC."

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

Dalpiciclib Combined with Letrozole as Neoadjuvant Therapy for Stage II-III HR-Positive, HER2-Negative Breast Cancer: A Phase II Study (SABCS 2025) - P2 | "This study aims to explore the efficacy and safety of dalpiciclib plus letrozole in patients with stage II-III HR+/HER2- BC. In this single-arm, open-label study (NCT05512416), early or locally advanced HR+/HER2- BC patients received six 28-day cycles of dalpiciclib (150 mg orally, once daily on days 1-21) plus letrozole (2.5 mg orally, once daily), with or without goserelin (3.6 mg, intramuscularly). Our results showed that dalpiciclib plus letrozole demonstrates a promising safety profile and antitumor activity in HR+/HER2− early/locally advanced BC, with significant suppression of proliferation (Ki‑67). These results support its potential as a fully oral, chemotherapy-free neoadjuvant regimen. Further studies are warranted to confirm these preliminary results."

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

An Exploratory Clinical Trial of CDK4/6 Inhibitor Dalpiciclib Combined with Aromatase Inhibitors as Neoadjuvant Therapy for Stage II-III HR-positive HER2-negative Breast Cancer (SABCS 2025) - "Participants receive dalpiciclib 150 mg/d (d1-21 every 28 days) + AIs (letrozole 2.5 mg/d, anastrozole 1 mg/d, or exemestane 25 mg/d); premenopausal women add ovarian suppression (goserelin/leuprolide). Conclusion Dalpiciclib combined with AIs demonstrates promising efficacy and manageable toxicity as neoadjuvant therapy for stage II-III HR+/HER2- breast cancer, offering a new chemotherapy-free option. Future research should focus on biomarker-guided patient selection, long-term outcomes assessment, and comparative trials with other neoadjuvant therapies, aiming to improve the treatment paradigm for HR+/HER2- breast cancer."

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

Ki-67-guided stratification and resistance mechanism analysis of CDK4/6 inhibitor therapy following adaptiveneoadjuvant endocrine treatment in HR+/HER2− breast cancer (SABCS 2025) - P4 | "Based on post-treatment Ki-67 levels (cut-off: 10%), patients were stratified into two groups: (A) AI-responsive (Ki-67 ≤10%), who proceeded directly to surgery; and (B) AI-nonresponsive (Ki-67 >10%), who received an additional cycle of AI combined with the CDK4/6i dalpiciclib prior to surgery... In patients initially nonresponsive to AI therapy, the addition of CDK4/6i significantly reduced Ki-67 levels, indicating that these individuals may benefit from intensified CDK4/6i-based therapy. The malignant epithelial C2 cell cluster and FUT6 were identified as potential therapeutic targets associated with CDK4/6i resistance. Moreover, persistent or emerging PIK3CA and TP53 mutations during adaptive therapy may serve as molecular indicators of resistance to sequential AI and CDK4/6i treatments."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CD8 • HER-2 • PIK3CA • SERPINA6 • TP53

Chemotherapy-free neoadjuvant strategy in HR+/HER2- breast cancer: CDK4/6 inhibitors plus endocrine therapy show comparable efficacy to chemotherapy-sequenced approach (SABCS 2025) - "Of these, 45 received ET + CDK4/6 inhibitor (ribociclib [n=21], abemaciclib [n=16], dalpiciclib [n=7], palbociclib [n=1]). Primary ET + CDK4/6 inhibitor demonstrated comparable efficacy to chemotherapy-sequenced therapy in HR+/HER2- breast cancer, particularly in patients with low Ki-67. These results support the feasibility of chemotherapy-free neoadjuvant strategies for select HR+/HER2− patients, potentially minimizing chemotherapy-related toxicity without compromising treatment efficacy."

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

DARLING-02: Dalpiciclib Plus AI (Neoadjuvant Endocrine Therapy) Compared With Neoadjuvant Chemotherapy in Early Breast Cancer （EBC） (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Hebei Medical University Fourth Hospital | Trial completion date: Dec 2025 ➔ Dec 2028 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Head-to-Head • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Pyrotinib combined with dalpiciclib in the treatment of refractory advanced HER2-positive gastric cancer or solid tumors: Safety and efficacy results from a phase Id trial (ESMO Asia 2025) - P1 | "Pyrotinib combined with dalpiciclib showed acceptable safety profile and encouraging efficacy in refractory advanced HER2-positive GC, even for patients pretreated with anti-HER2 ADCs."

Clinical • Metastases • Gastric Cancer • Oncology • Solid Tumor • HER-2