A Study of SHR-A1921 for Injection in Subjects With Advanced Solid Tumours

A Phase 1 Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-A1921 in Subjects With Advanced Malignant Solid Tumour .

To assess the safety and tolerability of SHR-A1921 in patients with advanced solid tumours, to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D) of SHR-A1921

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: SHR-A1921

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Quanren Wang, Ph.D; Phone Number: 86-021-61053363; Email: quanren.wang@hengrui.com
• Study Contact Backup: Name: Di Zong, MS; Phone Number: 86-010-67166319; Email: di.zong@hengrui.com

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. Voluntary participation and written informed consent；
2. Aged 18-75 years (inclusive), males and females;
3. Consents to provide tumor tissue samples;
4. Subjects must have histologically or clinically confirmed advanced and/or metastatic malignancies for which failure of standard treatment or lack of effective standard treatment;
5. At least one measurable lesion according to RECIST v1.1;
6. ECOG score of 0-1;
7. Expected survival ≥ 12 weeks;
8. Adequate bone marrow reserve and organ function ；
9. For female patients of childbearing potential or male patients with partners of childbearing potential who are not sterilized by surgical operations, they are required to use a medically approved contraceptive measure during the study treatment period and within 3 months after the end of the study treatment; For female patients of childbearing potential who are not sterilized by surgical operations, they must have a negative serum HCG test result within 72 h prior to study enrollment; and they must not be in the lactation period;

Exclusion Criteria:

1. Known and untreated central nervous system (CNS) or leptomeningeal metastases;
2. Macrovascular invasion based on imaging;
3. Cancerous ascites, pleural effusion or pericardial effusion with clinical symptoms;
4. Has a history of a second malignancy;
5. History of immunodeficiency disease or organ transplant;
6. Uncontrolled cardiac diseases or symptoms;
7. Has a history of non-infectious ILD/pneumonitis that required steroids, or has current ILD/pneumonitis;
8. Has a history of active chronic enteritis 6 weeks prior to the initiation of the study treatment or intestinal obstruction, gastrointestinal perforation 3 months prior to the initiation of the study treatment;
9. Has a history of Grade≥2 bleeding 4 weeks prior to the initiation of the study treatment or is current receiving anticoagulation therapy;
10. Subjects with active hepatitis B or active hepatitis C;
11. Subjects who have received systemic anti-tumor treatments 4 weeks prior to the initiation of the study treatment.
12. Has unresolved toxicities from previous anticancer therapy.
13. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of SHR-A1921;
14. Subjects with other potential factors that may affect the study results or result in the premature discontinuation as determined by the investigator, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, or family or social factors that could affect the safety of the patients.

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-A1921	Drug: SHR-A1921; Treatment group: Subjects will receive an intravenous infusion of SHR-A1921 in a dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limited Toxicity (DLT)		21 Days (first cycle)
Maximum Tolerable Dose (MTD)		21 Days (first cycle)
Recommended phase II dose (RP2D)		Screening up to dose escalation and expansion study completion, appropriately to 1 year
Adverse Events	Incidence and grade of adverse events as assessed by CTCAE v5.0	Screening up to study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach maximum concentration (Tmax) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Maximum concentration (Cmax) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Area under the concentration-time curve from time zero to the time of the last quantifiable time point t (AUC0-t) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-t) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Terminal half-life (t1/2) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Total body clearance (CL) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Volume of distribution at steady state (Vss) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Mean residence time (MRT) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Maximum steady-state drug concentration during a dosage interval (Css, max) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Minimum steady-state drug concentration during a dosage interval (Css, min) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Accumulation ratio (Rac) of SHR-A1921、total antibody	Screening up to end of treatment, an average of 1 year
Anti-drug antibody(ADA) level of SHR-A1921	Screening up to 90 days after the last dose, an average of 1 year
Objective Response Rate (ORR) assessed by site investigator as per RECIST 1.1	Screening up to study completion, an average of 1 year
Duration of Response (DoR) assessed by site investigator as per RECIST 1.1	Screening up to study completion, an average of 1 year
Disease Control Rate (DCR) assessed by site investigator as per RECIST 1.1	Screening up to study completion, an average of 1 year
Progression-Free Survival (PFS) assessed by site investigator as per RECIST 1.1	Screening up to study completion, an average of 1 year
Overall Survival (OS)	Screening up to study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 31, 2021
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-A1921-I-101

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