Phase I Study of SHR-A2102 in Patients With Advanced Solid Tumors

An Open-Label, Single-Arm, Multi-Center Phase I Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of SHR-A2102 in Patients With Advanced Solid Tumors

The study was designed to evaluate the efficacy, safety, and pharmacokinetics of SHR2102 in patients with advanced solid tumors. The objective of this study was to determine the dose-limiting toxicity, maximum tolerance and recommended dose of SHR-A2102 in phase II study.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: SHR-A2102

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fei Luo; Phone Number: +0518-81220121; Email: fei.luo@hengrui.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Hua Zhong

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able and willing to provide a written informed consent;
2. Age ≥18 years old, gender unlimited;
3. The physical status score of the Eastern Tumor Cooperative Group (ECOG) was 0 ~ 1;
4. Life expectancy Predicted survival ≥3 months;
5. Histologically or cytologically confirmed advanced or metastatic malignant tumor; Patients with advanced solid tumors confirmed by pathology who have failed or been intolerant to standard treatment, have no standard treatment or refuse standard treatment;
6. There is at least one measurable lesion that meets the RECIST 1.1 criteria.

Exclusion Criteria:

1. Plan to receive any other antitumor therapy during this trial;
2. Receiving other investigational drugs or treatments that are not on the market within 4 weeks prior to the initial administration of the study drug;
3. Received antitumor therapy such as chemotherapy, radiotherapy, biotherapy, targeted therapy, or immunotherapy within 4 weeks prior to first administration of the study drug (nitrosourea or mitomycin C within 6 weeks prior to first administration; Oral fluorouracil within 2 weeks prior to initial first administration); Palliative radiotherapy or local therapy within 2 weeks before first administration use of the study drug;
4. Had major surgery other than diagnosis or biopsy within 4 weeks prior to the study's initial dosing;
5. Treatment with CYP3A4, CYP2D6, P-gp or BCRP booster or inducer is less than 5 drug half-life from the date of first administration;
6. According to NCI-CTCAE v5.0, adverse events caused by previous antitumor therapy did not recover to ≤ grade 1 (except hair loss; In the judgment of the investigator, after consultation with the sponsor, some tolerable chronic grade 2 toxicity may be excluded);
7. Inadequately treated central nervous system (CNS) metastases, or the presence of uncontrolled or symptomatic active CNS metastases, may be characterized by the presence of clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, pia meningeal disease, and/or rapid progression. Patients with CNS metastases that have been adequately treated and whose neurological symptoms return to baseline at least 4 weeks prior to randomization (except for residual signs or symptoms associated with CNS treatment) may be enrolled. In addition, subjects must either stop corticosteroids or receive prednisone (or an equivalent dose of another corticosteroid) at least 4 weeks prior to randomization;
8. Any other malignancies, excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix, etc. within 5 years prior to initial administration;
9. A history of clinically significant lung disease (such as interstitial pneumonia, radiation pneumonia, pulmonary fibrosis) or chest imaging during screening suggests any such disease;
10. Severe infections that require intravenous antibiotic, antiviral or antifungal control;
11. Active HBV or HCV infection (HBsAg positive and viral copy number ≥2000 IU/mL, HCV antibody positive and HCV RNA higher than the lower limit of detection method);
12. History of immunodeficiency (including HIV positive, other acquired or congenital immunodeficiency diseases) or organ transplantation;
13. Concomitant diseases (such as severe diabetes, thyroid disease, and psychosis) or any other conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the patient's ability to complete the study.

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: SHR-A2102	Drug: SHR-A2102; SHR-A2102 was given intravenously. Patients may continue to use SHR-A2102 until disease progression or unacceptable toxicity occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Adverse events are assessed by CTCAE v5.0	24 months
Maximum tolerated dose (MTD)	MTD is defined as the maximum dose within the first 3 weeks of multiple dosing that does not exceed the proportion of subjects who develop DLT as specified in the protocol's BOIN design.	12 weeks
Recommended Phase 2 dose (RP2D)	RP2D will be determined based on the available data for toxicity and PK.	24 months
Dose Limiting Toxicity (DLT)	Adverse events that occurred during the DLT observation period (the first period of study administration, a total of 21 days) that were determined to be related to the study drug (see protocol for details).	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)		24 months
Peak plasma concentration (Cmax)		12 weeks
Area under the plasma concentration versus time curve (AUC）		12 weeks
T1/2 (Half-life)	The time required for the plasma concentration of a drug to be reduced by 50%	12 weeks
Immunogenicity: Number of subjects with anti-SHR-A2102 antibody (ADA), incidence, occurrence time, duration, etc		12 weeks
duration of response (DoR)		24 months
disease control rate (DCR)		24 months
progression-free survival (PFS)		24 months
overall survival (OS)		24 months

Collaborators and Investigators

• Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 28, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-A2102-I-102

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