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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05349409
• Other study ID #: SHR-A1811-?-201
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: June 9, 2022
• Est. completion date: May 31, 2025

Study information

• Verified date: June 2022
• Source: Suzhou Suncadia Biopharmaceuticals Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 212
• Est. completion date: May 31, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• SHR-A1811
SHR-A1811 for Injection: Given IV.
• Fluzoparib Capsule
Fluzoparib Capsule: Given PO.

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	C3h	PK concentration of Fluzoparib Capsule	3 hour after first dose of Fluzoparib Capsule in C2D1
Secondary	AUC0-t	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
Secondary	Cmin	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
Secondary	Cmax	PK parameters of SHR-A1811 for Injection	the date of first dose to 30 days after last dose
Secondary	ADA	Anti-drug antibody, Immunogenicity of SHR-A1811 for Injection	the date of first dose up to 90 days after last dose
Secondary	NAb	Neutralizing Antibody, Immunogenicity of SHR-A1811 for Injection	the date of first dose up to 90 days after last dose