HS-20089 Combination Treatment in Subjects With Advanced Solid Tumors

NCT06336707 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HS-20089-103
• Study Type: interventional
• Target: 1,048
• Locations: 1 country
• Sites: 1

Brief Summary

HS-20089 is an investigational antibody-drug conjugate (ADC) composed of a humanized IgG1 anti-B7-H4 monoclonal antibody conjugated to the topoisomerase I inhibitor payload via a protease-cleavable linker, with an average drug-to-antibody ratio of about 6. This is a phase Ⅰ, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of HS-20089 in combination with other antitumor agents (Adebrelimab with or without platinum; Bevacizumab with or without platinum) in subjects with advanced solid tumors.

Conditions

Advanced Solid Tumors

Keywords

HS-20089; B7-H4; Antibody-drug Conjugate; Combination Therapy

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-20089 in combination therapy

  To determine the MTD or MAD of HS-20089 in each combination therapy.

  Up to day 21 from the first dose

Secondary Outcomes (11)

• Incidence and severity of adverse events (AEs)

  From the first dose to 90 days after the end of treatment

• Observed maximum plasma concentration (Cmax) of HS-20089

  From pre-dose to 14 days after the first dose of HS-20089 on Cycle 1 (each cycle is 21 days).

• Time to reach maximum plasma concentration (Tmax) of HS-20089 following the first dose

  From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days).

• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20089

  From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days).

• Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089

  From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days).

Study Arms (4)

HS-20089 and Adebrelimab

EXPERIMENTAL

Drug: HS-20089; Drug: Adebrelimab

HS-20089, Adebrelimab and cisplatin / carboplatin

EXPERIMENTAL

Drug: HS-20089; Drug: Adebrelimab; Drug: Cisplatin / carboplatin

HS-20089 and Bevacizumab

EXPERIMENTAL

Drug: HS-20089; Drug: Bevacizumab

HS-20089, Bevacizumab and cisplatin / carboplatin

EXPERIMENTAL

Drug: HS-20089; Drug: Bevacizumab; Drug: Cisplatin / carboplatin

Interventions

HS-20089 DRUG

Intravenous infusion

HS-20089 and Adebrelimab; HS-20089 and Bevacizumab; HS-20089, Adebrelimab and cisplatin / carboplatin; HS-20089, Bevacizumab and cisplatin / carboplatin

Adebrelimab DRUG

Intravenous infusion

HS-20089 and Adebrelimab; HS-20089, Adebrelimab and cisplatin / carboplatin

Bevacizumab DRUG

Intravenous infusion

HS-20089 and Bevacizumab; HS-20089, Bevacizumab and cisplatin / carboplatin

Cisplatin / carboplatin DRUG

Intravenous infusion

HS-20089, Adebrelimab and cisplatin / carboplatin; HS-20089, Bevacizumab and cisplatin / carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 18 years or older (≥18 years).
• Patients diagnosed with pathologically confirmed advanced solid tumors.
• Subjects have at least one target lesion as assessed per the RECIST 1.1. Patients with only brain and/or bone lesions as target lesions are ineligible.
• Agree to provide fresh or archival tumor tissue
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1 and no deterioration within 2 weeks before the first dose.
• Have a life expectancy of at least 12 weeks.
• Female subjects of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent until 6 months after the last dose; male subjects must agree to use barrier contraception (i.e. condoms) from signing the informed consent to 6 months after the last dose.
• Female subjects must have a negative pregnancy test within 7 days prior to the first dose (for subjects with tumor related abnormal elevation of human chorionic gonadotropin \[HCG\], an ultrasound of uterus and appendages should be performed within 7 days prior to the first dose to rule out pregnancy), or demonstrate no risk for pregnancy.
• Subject must be voluntarily enrolled in this clinical trial, be able to understand the study procedures and to sign written informed consent.

You may not qualify if:

• Have received or is currently receiving the following treatment: B7-H4-targeted therapies; Have received any of cytotoxic chemotherapy drugs, investigational drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 14 days prior to the first dose of study drug; or need to continue these drugs during the study.
• Presence of Grade ≥ 2 toxicities as per Common Terminology Criteria for Adverse Events due to prior anti-tumor therapy.
• Presence of pleural/abdominal effusion requiring clinical intervention.
• Known history of other primary malignancy.
• Evidence of brain metastasis and/or cancerous meningitis
• Inadequate bone marrow reserve or hepatic/renal functions.
• Cardiological examination abnormality.
• Severe, uncontrolled or active cardiovascular disorders.
• Serious or poorly controlled diabetes.
• Serious or poorly controlled hypertension.
• Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose of study treatment.
• Serious infections within 4 weeks prior to the first dose.
• Have received systemic glucocorticoid therapy for more than 7 days within 28 days prior to the first dose study treatment, or require chronic (≥ 7 days) use of systemic glucocorticoids during the study, or have other acquired, congenital immunodeficiency disorders, or a history of organ transplantation.
• Presence of active infectious diseases such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus infection, etc.
• Current hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or more severe cirrhosis.

Sponsors & Collaborators

• Hansoh BioMedical R&D Company: lead

Study Sites (1)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Shanghai, Shanghai Municipality, 430000, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab; Cisplatin; Carboplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

Ding Ma, PhD

CONTACT

(0086)13886090620; dma@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 29, 2024
• Study Start: April 11, 2024
• Primary Completion: April 8, 2026
• Study Completion (Estimated): April 8, 2028
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

CN (1)