A Study of HS-20089 in Patients With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20089 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263479
• Other study ID #: HS-20089-101
• Status: Recruiting
• Phase: Phase 1
• Start date: January 5, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Hansoh BioMedical R&D Company
• Contact: Jiong Wu, PhD
• Phone: 13601637369
• Email: wujiong1122[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HS-20089 is a novel DAR-6 antibody-drug conjugate （ADC） targeting B7-H4. In preclinical studies, it inhibited tumor cell growth expressing B7-H4 in vitro and in vivo. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-20089 in Patients With Advanced Solid Tumors.

Description:

This is a Phase 1a/1b open-label, multicenter study with dose escalation and dose expansion cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of HS-20089 in patients with advanced solid tumors. The Dose Escalation will include an initial accelerated titration design followed by a Bayesian optimal interval (BOIN) design. Enrollment into Dose Expansion will begin after identification of the MTD and/or MAD in Phase 1a. In Phase 1b, preliminary efficacy will be evaluated in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 177
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men or women aged more than or equal to (=) 18 years

2. Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable

3. Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter = 10 mm in the baseline period (in case of lymph nodes, the shortest axis = 15 mm is required)

4. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks

5. Estimated life expectancy greater than (>) 12 weeks

6. Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential

7. Sign Informed Consent Form

Exclusion Criteria:

1. Treatment with any of the following:

1. Previous or current treatment with drugs targeting B7-H4

2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug

3. Radiotherapy with a limited field of radiation 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 of the first dose.

4. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.

5. Known and untreated, or active central nervous system metastases.

2. Existing abnormal CTCAE=grade 2 resulted from previous treatment

3. History of other malignancy

4. Inadequate bone marrow reserve or organ function

5. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV

6. History of hypersensitivity to any active or inactive ingredient of HS-20089.

7. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

8. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• HS-20089 (Phase Ia:Dose escalation )
Participants will receive HS-20089 in 21 day dosing cycles. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
• HS-20089 (Phase Ib: Dose expansion)
IV administration of HS-20089 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.

Locations

Country	Name	City	State
China	Fudan University Cancer Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Hansoh Biomedical Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of HS-20089	To determine the MTD for further evaluation of IV administration of HS-20089 in subjects with advanced solid tumors.	3 weeks after initiation of treatment
Secondary	Incidence and severity of treatment-emergent adverse events	The CTCAE criteria will be used to assess adverse events on this trial.	Baseline through study completion(90 days after last dose)
Secondary	Observed maximum plasma concentration (Cmax) after single dose of HS-20089	Cmax will be obtained after single dose of HS-20089 on Day 1.	From pre-dose to 120 hours after single dose on Day 1
Secondary	Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-20089	Cmax ss will be obtained on Day 1 of dosing in the 21-Day cycle of therapy.	From pre-dose to 24 hours after the dose on Day 1 of the 21-Day cycle of therapy
Secondary	Apparent terminal half-life (t1/2) after single dose of HS-20089	Apparent terminal half-life is the time measured for the concentration to decrease by one half.	From pre-dose to 120 hours after single dose on Day 1
Secondary	Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-20089	Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ).	From pre-dose to 24 hours after single dose on Day 1
Secondary	Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-20089	Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ).	From pre-dose to 120 hours after single dose on Day 1
Secondary	Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8) after single dose of HS-20089	AUC0-8 was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ ?z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and ?z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.	From pre-dose to 120 hours after single dose on Day 1
Secondary	To further evaluation of the anti-tumor activity of HS-20089 by assessment of objective response rate (ORR)	Anti-tumor efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -28 to -1). For patients that continue on repeating 21-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks of therapy. ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.	From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (=4 weeks), until the date of disease progression or withdrawal from study,up to 2 years
Secondary	Anti-drug Antibodies (ADA) of HS-20089	Number of participants who test positive for ADA to HS-20089 will be reported.	Baseline through study completion(90 days after last dose)