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

Phase 1

Recruiting

• Conditions: Advanced Breast Cancer
• Interventions: Drug: SHR-A1811; Drug: Ritonavir; Drug: Itraconazole

• Registration Number: NCT06710990
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-25
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-02
• Study Start: 2025-02-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-03-28
• Primary Completion: 2025-06
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: SHR-A1811 + Ritonavir	SHR-A1811	-
Cohort 1: SHR-A1811 + Ritonavir	Ritonavir	-
Cohort 2: SHR-A1811 + Itraconazole	SHR-A1811	-
Cohort 2: SHR-A1811 + Itraconazole	Itraconazole	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (2)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China