Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Gastric and Gastroesophageal Junction Adenocarcinoma, HS-20093
Brief summary
HS-20093 is a humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. This is a phase 1b, open-label, multi-center study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of HS-20093 in patients with advanced gastric and gastroesophageal junction adenocarcinoma.
Detailed description
The first approximately 20 eligible participants who meet the inclusion criteria and do not meet the exclusion criteria will receive intravenous infusion of 8.0 mg/kg HS-20093 once every three weeks (Q3W). Treatment will continue until objective disease progression or other treatment discontinuation criteria are met. Based on preliminary safety, efficacy, and pharmacokinetic data, the sponsor may decide whether subsequent participants will continue the current dosing regimen (8.0 mg/kg, Q3W), switch to a lower dose (e.g., 6.0 mg/kg, Q3W), a higher dose (e.g., 10.0 mg/kg, Q3W), or transition to a dosing frequency of once every two weeks (with a single dose not exceeding 6.0 mg/kg).
Interventions
Intravenous (IV) infusion of HS-20093 Q3W; Participants will receive continuous treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.
Sponsors
Hansoh BioMedical R&D Company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least age of 18 years at screening, with no restrictions on gender. 2. Signed and dated Informed Consent Form. 3. Participants with pathologically or cytologically confirmed locally advanced unresectable or metastatic GC/GEJC, who have failed, or intolerant to standard therapies. 4. At least one extra measurable lesion according to RECIST 1.1. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1. 6. Estimated life expectancy \>12 weeks. 7. Agree to provide fresh or archival tumor tissue. 8. Good organ function. 9. Female subjects must not be pregnant at screening or have evidence of non-childbearing potential. 10. Men or women should be using adequate contraceptive measures throughout the study.
Exclusion criteria
1. Treatment with any of the following: * Previous or current treatment with B7-H3 targeted therapy. * Previous or current treatment with topoisomerase I inhibitors. * Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093 * Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093 * Local radiotherapy for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first scheduled dose of HS-20093 * Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study. * Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study. 2. Histology shows squamous cell carcinoma, undifferentiated carcinoma, or mixed tumors , such as adenosquamous carcinoma or other mixed tumors. 3. Any unresolved toxicities from prior therapy greater than Grade 1 according to CTCAE 5.0 or baseline status. 4. Presence of pleural effusion/ascites requiring clinical intervention. 5. Newly diagnosed brain metastases without treatment, or brain metastases that have not achieved stability despite treatment; presence of leptomeningeal metastasis or brainstem metastasis; presence of spinal cord compression. 6. History of other primary malignancies 7. Evidence of cardiovascular risk. 8. Severe, uncontrolled or active cardiovascular diseases. 9. Severe or poorly controlled hypertension. 10. Severe or poorly controlled diabetes. 11. Poorly controlled cancer-related pain. 12. The presence of active infectious diseases has been known: hepatitis B, hepatitis C and HIV. 13. Major surgery within 4 weeks prior to the first scheduled dose of HS-20093. 14. Active infection requiring therapeutic intravenous antibiotics within 2 weeks prior to the first dose. 15. Clinically significant bleeding symptoms or marked hemorrhagic tendency within 1 month prior to the first dose of HS-20093. 16. Serious arterial or venous thromboembolic events occurring within 3 months prior to the first dose of HS-20093. 17. Active tuberculosis. 18. History of known interstitial pneumonia or immune-mediated pneumonitis. 19. History of active or prior autoimmune disease requiring systemic treatment. 20. Severe malnutrition. 21. Current hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B. 22. Requires long-term glucocorticoid therapy. 23. Having undergone any major surgery within 4 weeks prior to the first dose. 24. Vaccination within 4 weeks prior to the first dose of HS-20093. 25. History of severe allergy. 26. Previous history of serious neurological or mental disorders. Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator. 27. Currently enrolled in or participating in any other clinical study involving investigational interventions or other types of interventional medical research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. | From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months. | ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1\[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by RECIST 1.1 criteria | From the first dose up to PD or death，whichever came first, assessed up to 24 months. | PFS was defined as the time from first dose or random assignment (if any) to PD or death from any cause |
| Unconfirmed ORR (uORR) | From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months. | The proportion of participants who achieve a CR or PR as assessed by the investigator according to the RECIST v1.1 criteria |
| Duration of response (DoR) | From the first dose up to PD or death, whichever came first, assessed up to 24 months. | the time from the date of first documented objective response (CR or PR as assessed by the investigator according to the RECIST v1.1 criteria) to the date of first documented PD or death (whichever occurs first). |
| Incidence and severity of adverse events (AEs) | From the first dose until 90 days after the last dose | AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\]. Any untoward medical occurrence in a clinical study participant, whether or not considered related to the medicinal product. Incidence and severity of AEs are assessed according to vital signs, laboratory variables, physical examination, electrocardiogram, etc. |
| Cmax of HS-20093 | At the end of Cycle 1 (each cycle is 21 days)" | The Cmax is the maximum observed drug concentration of HS-20093 |
| Tmax of HS-20093 | At the end of Cycle 1 (each cycle is 21 days)" | The Tmax is defined as time to reach maximum observed drug concentration of HS-20093 |
| AUC0-t of HS-20093 | At the end of Cycle 1 (each cycle is 21 days)" | The AUC0-t is defined as the area under the drug concentration-time curve during a dose interval time period(t) of HS-20093 |
| Incidence of anti-hs-20093 antibodies (ADAs) | From the first dose until 90 days after the last dose | Serum samples were collected for the determination of anti-drug antibody (ADA) at designated time points |
Countries
China
Outcome results
None listed