A Study of HS-20124 in Patients with Advanced Solid Tumors

Official title

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20124 in Patients with Advanced Solid Tumors

Overview

HS-20124 is a novel DAR-8 antibody-drug conjugate （ADC） targeting CDH6. In preclinical studies, it inhibited tumor cell growth expressing CDH6 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-20124 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-20124 in patients with advanced solid tumors.

The dose escalation will utilize rolling-6 design. In phase of dose expansion, preliminary efficacy will be evaluated in planned expansion cohorts that include patients with specific advanced solid tumor types.

Interventions

• Drug HS-20124 (Phase Ia：Dose escalation )
  Participants will receive HS-20124 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-20124 (Phase Ib: Dose expansion)
  Participants will receive HS-20124 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.

Primary outcome measures

• Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of complete response (CR) an [Time frame: 3 weeks after initiation of treatment]
• Ⅰb (Dose-Expansion Stage): Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Time frame: From the first dose up to PD or withdrawal from study, whichever came first.]

Secondary outcome measures (8)

• Incidence and severity of treatment-emergent adverse events [Time frame: From the first dose through 30 days post end of treatment]
• Observed maximum plasma concentration (Cmax) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Time to reach maximum plasma concentration (Tmax) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Terminal half-life (T1/2) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Percentage of participants with antibodies to HS-20124 in serum [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• ORR determined by investigators according to RECIST 1.1 (dose-escalation stage) [Time frame: during the intervention]
• Duration of response (DOR) determined by investigators according to RECIST 1.1 [Time frame: during the intervention]
• Progression-free survival (PFS) determined by investigators according to RECIST 1.1 [Time frame: From the randomization/first dose up to PD or death, whichever came first]

Eligibility criteria

Inclusion criteria

• At least age of 18 years at screening;
• Histologically or cytologically confirmed, locally advanced or metastatic solid tumors for which standard treatment either does not exist or has proven ineffective or unavailable or intolerable
• At least one extra-cranial measurable lesion according to RECIST 1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1
• Life expectancy >= 12 weeks
• Men or women should be using adequate contraceptive measures throughout the study;
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential
• Signed and dated Informed Consent Form

Exclusion criteria

1.Treatment with any of the following:

• Previous or current treatment with CDH6 targeted therapy
• Any cytotoxic chemotherapy and small molecule targeted anticancer drugs within 21 days or five half-livesprior to the first scheduled dose of HS-20124
• Prior treatment with a monoclonal antibody or investigational agents within 28 days prior to the first scheduled dose of HS-20124
• Radiotherapy with a limited field of radiation for palliation within 2 weeks, 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-20124
• Major surgery within 4 weeks prior to the first scheduled dose of HS-20124 2. Subjects with previous or concurrent malignancies 3. Inadequate bone marrow reserve or organ dysfunction 4. Evidence of cardiovascular risk 5. Evidence of current severe or uncontrolled systemic diseases 6. Evidence of mucosal or internal bleeding within 1 month prior to the first scheduled dose of HS-20124 7. Severe infection within 4 weeks prior to the first scheduled dose of HS-20124 8. Subjects with current infectious diseases 9. History of neuropathy or mental disorders 10. Pregnant or lactating female 11. History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to HS-20124 or any of the components of HS-20124

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

• Affiliated Cancer Hospital of Fudan University — Shanghai

Identifiers

NCT: NCT06763159 · HS-20124-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗