Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy

NCT05806671 | Unknown Phase 2

• 1 other identifier: OBU-BC-II-086
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the triplet combination of dalpiciclib, fulvestrant, and pyrotinib is safe and effective in the treatment of hormone receptor-positive, HER2-low locally advanced/metastatic breast cancer following treatment with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib abemaciclib or ribociclib). The study will employ a Bayesian Optimal Phase II (BOP2) design which explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs, and has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) as Assessed by the Investigator

  Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  From start date to date of first documentation of progression or death (assessed up to 12 months)

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  From start date to date of first documentation of progression or death (assessed up to 12 months)

• Clinical Benefit Rate (CBR)

  From start date to date of first documentation of progression or death (assessed up to 12 months)

• Overall Survival (OS)

  From start date to date of death (assessed up to 24 months)

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)

  From the signing of the informed consent until 28 days after the last dose of study medication up to 14 months

Study Arms (1)

Dalpiciclib, Fulvestrant With Pyrotinib

EXPERIMENTAL

Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg

Drug: Dalpiciclib; Drug: Pyrotinib; Drug: Fulvestrant

Interventions

Dalpiciclib DRUG

Dalpiciclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off

Also known as: SHR6390

Dalpiciclib, Fulvestrant With Pyrotinib

Pyrotinib DRUG

Pyrotinib 320mg/day orally continuously

Dalpiciclib, Fulvestrant With Pyrotinib

Fulvestrant DRUG

Fulvestrant 500mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

Dalpiciclib, Fulvestrant With Pyrotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
• Most recent tumor biopsy or surgical resection specimen must be either estrogen-receptor (ER) positive, progesterone receptors (PgR) positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines).
• HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP guidelines).
• Postmenopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin. Postmenopausal status is defined by any one of the following criteria:
• Prior bilateral oophorectomy.
• Age ≥60 years.
• Age \<60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of anti-estrogen therapy.
• Patient must have either measurable disease by RECIST 1.1 or only bone lesions in absence of measurable disease.
• Eastern Cooperative Group (ECOG) performance status of 0 or 1.
• Previously treated on CDK 4/6 inhibitor(palbociclib, abemaciclib or ribociclib) with AI for at least 6 months
• Adequate bone marrow and organ function.

You may not qualify if:

• Patient with symptomatic visceral disease or any disease burden.
• Patient has received more than one line of chemotherapy for advanced disease.
• Previous treatment with Dalpiciclib /Pyrotinib /ADCe for advanced disease.
• Progressed on more than one CDK 4/6 inhibitor
• Patients with persistent symptoms and unstable brain metastases;
• Any condition that makes the patient ineligible for endocrine therapy per the investigator's best judgment

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Cancer Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

dalpiciclib; pyrotinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 10, 2023
• Study Start: May 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)