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

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

Overview

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.

Detailed 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.

Interventions

• 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.
• Drug 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.

Primary outcome measures

• Maximum Tolerated Dose of HS-20089 [Time frame: 3 weeks after initiation of treatment]

Secondary outcome measures (9)

• Incidence and severity of treatment-emergent adverse events [Time frame: Baseline through study completion(90 days after last dose)]
• Observed maximum plasma concentration (Cmax) after single dose of HS-20089 [Time frame: From pre-dose to 120 hours after single dose on Day 1]
• Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-20089 [Time frame: From pre-dose to 24 hours after the dose on Day 1 of the 21-Day cycle of therapy]
• Apparent terminal half-life (t1/2) after single dose of HS-20089 [Time frame: From pre-dose to 120 hours after single dose on Day 1]
• Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-20089 [Time frame: From pre-dose to 24 hours after single dose on Day 1]
• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-20089 [Time frame: From pre-dose to 120 hours after single dose on Day 1]
• Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089 [Time frame: From pre-dose to 120 hours after single dose on Day 1]
• To further evaluation of the anti-tumor activity of HS-20089 by assessment of objective response rate (ORR) [Time frame: 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]
• Anti-drug Antibodies (ADA) of HS-20089 [Time frame: Baseline through study completion(90 days after last dose)]

Eligibility criteria

Inclusion criteria

• Men or women aged more than or equal to (≥) 18 years
• Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
• 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)
• ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
• Estimated life expectancy greater than (>) 12 weeks
• 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
• Sign Informed Consent Form

Exclusion criteria

• Treatment with any of the following:

• Previous or current treatment with drugs targeting B7-H4
• Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
• 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.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
• Known and untreated, or active central nervous system metastases.
• Existing abnormal CTCAE≥grade 2 resulted from previous treatment
• History of other malignancy
• Inadequate bone marrow reserve or organ function
• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
• History of hypersensitivity to any active or inactive ingredient of HS-20089.
• 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.
• Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Cancer Hospital — Shanghai

Identifiers

NCT: NCT05263479 · HS-20089-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗