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

NCT06710990 | Recruiting Phase 1

• 1 other identifier: SHR-A1811-105
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• 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.

Study Arms (2)

Cohort 1: SHR-A1811 + Ritonavir

EXPERIMENTAL

Drug: SHR-A1811; Drug: Ritonavir

Cohort 2: SHR-A1811 + Itraconazole

EXPERIMENTAL

Drug: SHR-A1811; Drug: Itraconazole

Interventions

SHR-A1811 DRUG

SHR-A1811

Cohort 1: SHR-A1811 + Ritonavir; Cohort 2: SHR-A1811 + Itraconazole

Ritonavir DRUG

Ritonavir

Cohort 1: SHR-A1811 + Ritonavir

Itraconazole DRUG

Itraconazole

Cohort 2: SHR-A1811 + Itraconazole

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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;
• 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.
• 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.);
• Having contraindications to ritonavir or itraconazole use;
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (2)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510200, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Interventions

Ritonavir; Itraconazole

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Piperazines

Central Study Contacts

Meijing Yu

CONTACT

+86-021-61053363; meijing.yu@hengrui.com

Yanyan Zhang

CONTACT

+86-021-61053363; yanyan.zhang@hengrui.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: December 2, 2024
• Study Start: February 17, 2025
• Primary Completion: June 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

CN (2)