Investigation of Drug-drug Interaction of Ritonavir and Itraconazole on the Pharmacokinetics of SHR-A1811 in Subjects With HER2-expressing Advanced Breast Cancer

A Multicenter, Open-label, Fixed-sequence Study to Evaluate Drug-drug Interaction of Ritonavir and Itraconazole on the Pharmacokinetics of SHR-A1811 in Subjects With HER2-expressing Advanced Breast Cancer

The study is being conducted to evaluate the pharmacokinetics and safety of SHR-A1811 monotherapy and in combination with Ritonavir or Itraconazole in subjects with HER2-expressing advanced breast cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Itraconazole; Drug: SHR-A1811; Drug: Ritonavir

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510200
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ECOG score of 0 or 1;
2. Expected survival of not less than 3 months;

3. Important organ functions meet the following criteria:

   • Absolute neutrophil count (ANC) ≥1.5×109/L (1,500/mm3);
   • Platelet count (PLT) ≥100×109/L (100,000/mm3);
   • Hemoglobin (Hgb) ≥9.0 g/dL (90g/L);
   • Albumin level ≥3.0 g/dL;
   • Total serum bilirubin ≤1.5× the upper limit of normal (ULN);
   • Prothrombin time and activated partial thromboplastin time (aPTT) ≤1.5×ULN;
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (for patients with liver metastasis, ALT and AST ≤5×ULN);
   • Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min;
   • QTcF ≤470 msec;
   • Left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

1. Known active central nervous system metastases that have not been treated with surgery or radiation, except those that have been stable for at least 1 month after treatment and have discontinued corticosteroids for >2 weeks;
2. Having cardiac diseases, such as severe/unstable angina, symptomatic congestive heart failure (NYHA II-IV), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, myocardial infarction within 6 months before the first administration, etc.
3. Known severe allergic history to any component of the SHR-A1811 product (ADC, total antibody, unconjugated toxin SHR169265 or its excipients), or hypersensitivity to humanized monoclonal antibody products (such as trastuzumab, pertuzumab, etc.);
4. Having contraindications to ritonavir or itraconazole use;
5. Having one or more factors that affect oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction, partial or total gastrectomy, etc.), or having active gastrointestinal diseases or other diseases that may significantly affect drug absorption, distribution, metabolism, or excretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: SHR-A1811 + Ritonavir	Drug: SHR-A1811; SHR-A1811; Drug: Ritonavir; Ritonavir
Experimental: Cohort 2: SHR-A1811 + Itraconazole	Drug: Itraconazole; Itraconazole; Drug: SHR-A1811; SHR-A1811

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The maximum concentration (Cmax) for SHR-A1811	Cycle 2 and Cycle 3. Each cycle is 21 days.
The maximum concentration (Cmax) for payload	Cycle 2 and Cycle 3. Each cycle is 21 days.
Area under the concentration curve from time 0 to 16 days (AUC0-16d) for SHR-A1811	Cycle 2 and Cycle 3. Each cycle is 21 days.
Area under the concentration curve from time 0 to 16 days (AUC0-16d) for payload	Cycle 2 and Cycle 3. Each cycle is 21 days.

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum plasma concentration (Tmax)	Cycle 2 and Cycle 3. Each cycle is 21 days.
Terminal half-life (t1/2)	Cycle 2 and Cycle 3. Each cycle is 21 days.
Area under the concentration curve from time 0 to infinity (AUCinf)	Cycle 2 and Cycle 3. Each cycle is 21 days.
Clearance (CL)	Cycle 2 and Cycle 3. Each cycle is 21 days.
Volume of distribution at steady state (Vss)	Cycle 2 and Cycle 3. Each cycle is 21 days.
Incidence and severity of adverse events	From the beginning of screening period to approximately 3 months after the last dose.

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Actual): October 15, 2025
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Triazoles; Piperazines; Ritonavir; Itraconazole
• Other Study ID Numbers: SHR-A1811-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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