Clinical trial NCT05701709: Phase I Study of SHR-A2102 in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-27
Enrollment: 395
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SHR-A2102 single arm
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 24 months
measure: Maximum tolerated dose (MTD)
timeFrame: 12 weeks
measure: Recommended Phase 2 dose (RP2D)
timeFrame: 24 months
measure: Dose Limiting Toxicity (DLT)
timeFrame: 3 weeks
Secondary outcomes:
measure: Peak plasma concentration (Cmax)
timeFrame: 12 weeks
measure: Area under the plasma concentration versus time curve (AUC）
timeFrame: 12 weeks
measure: T1/2 (Half-life)
timeFrame: 12 weeks
measure: Immunogenicity: Number of subjects with anti-SHR-A2102 antibody (ADA), incidence, occurrence time, duration, etc
timeFrame: 12 weeks
measure: Objective response rate (ORR)
timeFrame: 24 months
measure: duration of response (DoR)
timeFrame: 24 months
measure: disease control rate (DCR)
timeFrame: 24 months
measure: progression-free survival (PFS)
timeFrame: 24 months
measure: overall survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
References: