Exploration of Dalpiciclib + Chidamide in HR+/HER2- Advanced Breast Cancer After Failure of CDK4/6 Inhibitor: a Phase Ⅰb Study

A phase 1B study to explore the maximum tolerated dose (MTD) of dalpiciclib + chidamide in HR+/HER2- advanced breast cancer after the failure of CDK4/6 inhibitor therapy

Study Overview

• Status: Completed
• Conditions: HR+/HER2- Advanced Breast Cancer
• Intervention / Treatment: Drug: Dalpiciclib; Drug: Chidamide

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100071
      • The Fifth Medical Center of PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects voluntarily participate in this study and sign the informed consent form
2. Faged ≥ 18 years.
3. ECOG PS score: 0-2 points.
4. Expected survival ≥ 3 months.
5. Regionally recurrent or metastatic disease with histologically or cytologically confirmed ER+ and/or PR+ (≥ 10%), HER2- breast cancer that is not suitable for definitive excision or radiation therapy.
6. Previously received antitumor therapy: 1) previously received ≤1 line of chemotherapy for recurrent or metastatic breast cancer; 2) Disease recurrence and/or metastasis during or after treatment with Palbociclib or Abemaciclib or Ribociclib in the setting of (neo-)adjuvant therapy, or during treatment with palbociclib or Abemaciclib or Ribociclib in a metastatic setting or after disease progression; 3) No more than 3 lines of endocrine therapy have been previously received for recurrent or metastatic breast cancer. 4) Line number of previous chemotherapy ≤1 line
7. At least one extracranial measurable lesion as defined by RECIST v1.1;

8. The function of vital organs meets the requirements;

   • Absolute neutrophil count ≥ 1.5 × 10^9/L;
   • Platelets ≥ 90 × 10^9/L;
   • Hemoglobin ≥ 90g/L;
   • Total bilirubin (TBIL) ≤ 1.5 × ULN;
   • ALT and AST ≤ 2.5 × ULN;
   • Urea/blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN;
   • Left ventricular ejection fraction (LVEF) ≥ 50%;
   • The QT correction by the Fridericia formula (QTcF) is < 470 ms. INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.
9. Subject recovers from any AE related to previous antitumor therapy before the first administration of the study drug (Grade ≤ 1).

Exclusion Criteria:

1. Previously received treatment with histone deacetylase inhibitor (HDACi);
2. Previously received Dalpiciclib;
3. MRI or lumbar puncture confirmed leptomeningeal metastasis;
4. Central nervous system metastasis is confirmed by imaging; The following conditions will be excluded: 1) asymptomatic brain metastases without immediate radiotherapy or surgery; 2) Previously received local treatment (radiotherapy or surgery) for brain metastases, stable for at least 4 weeks, and no symptomatic treatment (including glucocorticoids, mannitol, bevacizumab, etc.) for more than 2 weeks with clinical symptoms;
5. The participants presented with visceral crisis (such as lymphangitis carcinomatosis, bone marrow replacement, leptomeningeal metastasis, diffuse liver metastasis with abnormal liver function), rapid disease progression, and that is not suitable for endocrine therapy;
6. Participants had ascites, pleural effusion and pericardial effusion with clinical symptoms at baseline, which required drainage within 4 weeks before the first medication;
7. Inability to swallow, intestinal obstruction, or other factors that affect medication administration and absorption;
8. Subjects that are diagnosed with any other malignancy within 5 years prior to the study, excluding non-melanoma skin cancer treated with radical therapy, basal or squamous cell skin cancer or carcinoma in situ of the cervix and papillary thyroid.
9. The subject has undergone major surgery or major trauma or is expected to undergo major surgery within 4 weeks before the start of treatment;
10. A known history of allergy to the drug ingredient of this protocol;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dalpiciclib + Chidamide; Dalpiciclib will be administered in a dose of 100 mg/d or 125 mg/d. Chidamide shall be designed in a dose of 25 mg/BIW or 20 mg/BIW

Drug: Dalpiciclib; Dalpiciclib: 100 mg/d or 125 mg/d, po., qd, administered on an empty stomach (fasting should be ensured at least 1 hour before and 1 hour after administration). The drug will be administered in a 28-day cycle, with continuously administration in the first 3 weeks (D1-21), and discontinuation in the fourth week (D22-28).; Other Names: SHR6390; Drug: Chidamide; Chidamide: 25 mg/BIW or 20 mg/BIW, po., q2w. The interval between doses should not be less than 3 days (e.g. Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.), administered 30 minutes after meals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Dalpiciclib + Chidamide	Bayesian optimal interval (BOIN) design method will be used in this clinical trial to determine the maximum tolerated dose (MTD).	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) of different dose groups	According to recist1.1 standard, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.	2 Years
Safety of different dose groups (incidence of treatment-related adverse events)	The severity of adverse events shall be determined according to CTCAE v5.0. During the trial, the adverse event record form should be truthfully filled in, including the occurrence time, severity, duration, measures taken and outcome of adverse events.	AE recorded from infromed consent to 28 days after treatment completion
PFS	The time from the date of randomization to the date of first documented progression or date of death from any cause, whichever came first.	2 Years

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital

Publications and helpful links

General Publications

• Zhou J, Wu X, Du Y, Xiao J, Kang X, Chen J, Wang X, Tai Y, Bian L, Zhang S, Pang Z, Li Y, Jiang Z, Xu X, Wang T. Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial. Nat Commun. 2026 Mar 20. doi: 10.1038/s41467-026-70650-6. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): December 30, 2025
• Study Completion (Actual): March 30, 2026

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Maximum Tolerated Dose; Chidamide; Dalpiciclib; the failure of CDK4/6 inhibitor therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; dalpiciclib
• Other Study ID Numbers: MA-BC-II-047

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No