AiRuiKang (dalpiciclib) / Jiangsu Hengrui Pharma - LARVOL DELTA

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

Cyclic kinase 4 and 6 inhibitor plus endocrine therapy (ET) as first-line therapies in advanced breast cancer: A patient-level data network meta-analysis (ESMO Asia 2025) - "In the first-line setting for HR+/HER2− advanced breast cancer, all CDK4/6 inhibitors combined with endocrine therapy significantly improve progression-free survival compared with endocrine therapy alone, with no significant differences observed among them."

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

Efficacy and safety of mecapegfilgrastim for prophylaxis of dalpiciclib-induced neutropenia in patients with advanced HR+/HER2- breast cancer: A multicenter, open-label, randomized controlled phase II trial (ESMO Asia 2025) - P2 | "Mecapegfilgrastim reduced the incidence of grade ≥3 dalpiciclib- induced neutropenia in the first cycle, thereby decreasing the rates of dalpiciclib interruption, dose reduction and discontinuation."

Clinical • Metastases • 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

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

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

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

Non-intravenous chemotherapy-sparing triplet of dalpiciclib/pyrotinib/endocrine therapy… (PLEASURABLE phase 2 trial) (ABC8 2025) - No abstract available

P2 data • Oncology

Dalpiciclib Plus Camrelizumab for HCC Patients Who Have Previously Received ICI Treatment (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Sun Yat-sen University

Checkpoint inhibition • New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

The Locally Active-Controlled Optimal Design: Applications in Oncology Clinical Studies. (PubMed, Biom J) - "Our novel approach avoids unrealistic distributional assumptions about response measurements. The resulting locally AC-optimal design minimizes the variance of the estimated matching dose of Dalpiciclib to Capecitabine and may unify Phase II and Phase III objectives by allowing evaluation of a higher Dalpiciclib dose with prespecified superiority."

Journal • Oncology

Clinical Study of Fluzoparib Combined with Dalpiciclib and Endocrine Neoadjuvant Therapy for gBRCA-Mutated HR+/HER2- Early-Stage Breast Cancer (ChiCTR) - P=N/A | N=30 | Not yet recruiting | Sponsor: Harbin Medical University Affiliated Cancer Hospital; Harbin Medical University Affiliated Cancer Hospital

New trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HER-2

An Exploratory Study of Concurrent or Sequential Radiotherapy Combined with Dalpiciclib plus Endocrine Therapy in Early-Stage or Locoregionally Advanced Hormone Receptor-Positive/HER2-Negative Breast Cancer (ChiCTR) - P2 | N=200 | Not yet recruiting | Sponsor: Shanxi Cancer Hospital; Shanxi Cancer Hospital

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Single arm, multicenter, exploratory phase II clinical study of new adjuvant therapy with Trastuzumab Deruxtecan for Injection for injection for early or locally advanced HR positive/HER2 low expression breast cancer with poor efficacy of dalpiciclib combined with endocrine therapy (ChiCTR) - P4 | N=30 | Not yet recruiting | Sponsor: Anyang Tumor Hospital; Anyang Tumor Hospital

New P4 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Efficacy and safety of Dalpiciclib in combination with endocrine adjuvant therapy for middle/high-risk HR-positive early stage breast cancer: a multicenter, prospective clinical study (ChiCTR) - P4 | N=2000 | Recruiting | Sponsor: Jilin Cancer Hospital; Jilin Cancer Hospital

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

Letter to the editor--efficacy and Safety of Neoadjuvant Treatment of Trastuzumab and Pyrotinib Plus Dalpiciclib in HR-negative/HER2-positive Breast Cancer an Exploratory, Open-label Phase II Study. (PubMed, Int J Surg) - No abstract available

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

Efficacy and safety of JS105, a selective inhibitor of mutant PI3Kα, in patients with advanced cancer (ESMO 2025) - P1, P1/2 | "The combination therapy study enrolled patients with HR-positive, HER2-negative advanced breast cancer to receive JS105 150 to 250 mg in combination with dalpiciclib and fulvestrant for a 28-day cycle. Among the 23 patients with PIK3CA mutations, the ORR and DCR were 39.1% and 87.0% (Table). Table: 466P The best overall response of two studies (Based on investigator assessment per RECIST 1.1) Monotherapy Study Combination Therapy Study Evaluable patients with PIK3CA mutation and measurable lesions, n 32 23 Best Overall Response, n (%) Complete Response (CR) 0 0 Partial Response (PR) 9 (28.1) 9 (39.1) Stable Disease (SD) 19 (59.4) 11 (47.8) Progressive Disease (PD) 4 (12.5) 3 (13.0) Objective Response Rate (ORR), %, (95% CI) 28.1 (13.7, 46.7) 39.1 (19.7, 61.5) Disease Control Rate (DCR), %, (95% CI) 87.5 (71.0, 96.5) 87.0 (66.4, 97.2) Conclusions JS105 monotherapy or combination therapy demonstrated a favorable safety profile and promising efficacy in patients..."

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

Matching-adjusted indirect comparison of bireociclib plus fulvestrant versus dalpiciclib Plus fulvestrant as second-line treatment of HR+/HER2- advanced breast cancer (ABC) (ESMO 2025) - P3 | "Conclusions This MAIC analysis suggests comparable efficacy between bireociclib and dalpiciclib when combined with fulvestrant in HR+/HER2- ABC patients who progressed on or after prior endocrine therapy. The two agents display distinct safety profiles, with dalpiciclib showing more severe hematological toxicities and bireociclib exhibiting more gastrointestinal adverse events."

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

DALPICICLIB COMBINED WITH NONSTEROIDAL AROMATASE INHIBITORS IN ESTROGEN RECEPTOR-POSITIVE RECURRENT/METASTATIC OVARIAN CANCER AND UTERINE NEOPLASMS: UPDATED RESULTS FROM A SINGLE-CENTER, SINGLE-ARM TRIAL (IGCS 2025) - P2 | "As the data cutoff (Apr. 17th, 2025), 30 pts with a median of one prior therapy for advanced disease were enrolled, including 9 with low-grade serous ovarian carcinoma (LGSOC), 12 with uterine EC, 8 with low-grade endometrial stromal sarcoma (LGESS) and 1 with uterine leiomyosarcoma (LMS). Twenty-five pts had received ≥1 efficacy assessment, and 76.0% achieved 12wPFS."

Clinical • Metastases • Endometrial Cancer • Leiomyosarcoma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Sarcoma • Solid Tumor • Uterine Cancer • Uterine Leiomyosarcoma • ER