A Trial of the Combination of SHR-A1811 and Fluzoparib in HER2-Expressing Cancers

A Phase Ⅰb/Ⅱ Clinical Study on the Dosage Exploration and Efficiency Expansion of SHR-A1811 for Injection in Combination With Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients

The study is being conducted to evaluate safety, tolerability and preliminary efficacy of SHR-A1811 for Injection in combination with Fluzoparib Capsule for HER2-expressing advanced solid tumors of patients. To explore the reasonable dosage of dosage regimen of combination therapy for HER2-expressing advanced malignant tumors of patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: SHR-A1811; Drug: Fluzoparib Capsule

• Study Type: Interventional
• Enrollment (Anticipated): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 410013
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female aged ≥18 years at the time of signing the ICF.
2. At least one measurable lesion that meets RECIST 1.1 criteria in case of solid tumors.
3. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
4. Life expectancy ≥12 weeks.
5. Adequate organ functions as defined.
6. Swallow the drug pills normally.

Exclusion Criteria:

1. patients with active meningeal metastasis, or brain metastasis without surgical treatment or radiotherapy.
2. Cancerous ascites and pleural effusion with clinical symptoms, which need puncture and drainage.
3. Prior malignancy (other than current malignant tumor) within 5 years before the first dose of study treatment.
4. History of autoimmune diseases.
5. Not well controllable and serve cardiovascular disease.
6. Prior lung disease with clinical significance.
7. Occurrence of ≥ grade 2 of bleeding event within 4 weeks before the first dose, or currently receiving the anticoagulation.
8. Active Hepatitis B and Hepatitis C; or serve infection with medication control.
9. The grade of toxicity from the prior anti-cancer therapy not decrease to ≤ 1.
10. Occurrence of intestinal obstruction and gastrointestinal perforation within 3 months before the first dose.

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: Treatment group; SHR-A1811, Fluzoparib	Drug: SHR-A1811; SHR-A1811 for Injection: Given IV.; Drug: Fluzoparib Capsule; Fluzoparib Capsule: Given PO.; Other Names: SHR-3162

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limited Toxicity	Dose Limited Toxicity of SHR-A1811 for Injection in combination with Fluzoparib Capsule in Dose Exploration Period	first dose of study medication up to 21 days
Recommended phase II dose	The Recommended phase II dose of SHR-A1811 for Injection in combination with Fluzoparib Capsule in Dose Exploration Period	first dose of study medication up to 21 days
ORR	Objective Response Rate, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients in indication expansion period	from the date of the first dose to the date of disease progression evaluated based on RECIST v1.1 criteria, or initiation of other anti-tumor treatment, whichever occurs first, up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DoR	Duration of response, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the firstly documented tumor response (evaluated based on RECIST v1.1 criteria) to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months
DCR	Disease control rate, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months
TTR	Time to Recovery, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the first dose to the date of treatment termination, up to 6 months
PFS	Progression-free survival, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months
OS	Overall survival, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the first dose to the date of death for any reason, up to 100 months
12 months' survival rate	Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients	from the date of the first dose up to 12 months
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs)	Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	from signature completion of ICF to 30 days after the last dose or to the beginning of the new anti-cancer therapy, up to 6 months
The occurrence rate of dose titration due to AE related with study medication	The occurrence rate of dose interruption, dose decrease and dose termination because of study drug related toxicity during the study	from signature completion of ICF to 30 days after the last dose or to the beginning of the new anti-cancer therapy, up to 6 months
Cmin	PK concentration of Fluzoparib Capsule	10 min before first dose of Fluzoparib Capsule in C1D8 to 10 min before first dose of Fluzoparib Capsule in C8D1
C3h	PK concentration of Fluzoparib Capsule	3 hour after first dose of Fluzoparib Capsule in C2D1
AUC0-t	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
Cmin	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
Cmax	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
ADA	Anti-drug antibody, Immunogenicity of SHR-A1811 for Injection	the date of first dose up to 90 days after last dose
NAb	Neutralizing Antibody, Immunogenicity of SHR-A1811 for Injection	the date of first dose up to 90 days after last dose

Collaborators and Investigators

• Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): May 31, 2025

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: SHR-A1811-Ⅱ-201

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