Clinical trial NCT06332170: ARTEMIS-101: A Study of HS-20093 Combinations in Patients With Advanced Solid Tumors
Official title: ARTEMIS-101: A Phase 1, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administration of HS-20093 in Combination With Other Anti-cancer Agents in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Hansoh BioMedical R&D Company
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents in patients with advanced solid tumor patients.

Detailed description: This is a phase 1, open-label, multi-center, dose-escalation and expansion, phase 1 study in Chinses subjects with advanced solid tumors. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents.

A total of 5 combination-treatments will be carried out in 3 cohorts. The target population of dose escalation part is patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.

All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of study drug. Subjects will be permitted to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists.

Eligibility criteria: Inclusion Criteria:

* At least age of 18 years at screening;
* Histologically or cytologically confirmed, locally advanced or metastatic solid tumors

  1. Dose escalation part will enroll advanced solid tumor for which standard treatment has proven ineffective or unavailable or intolerable.
  2. Dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.
* least one extra-cranial measurable lesion according to RECIST 1
* Agree to provide fresh or archival tumor tissue
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1
* Life expectancy \>= 12 weeks
* Agree to use medically accepted methods of contraception
* 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:

* Any of the following would exclude the subject from participation in the study:

treatment with any of the following: Previous or current treatment with B7-H3 targeted therapy Intolerable for any PD-L1 inhibitor, cetuximab, enzalutamide and cisplatin/ carboplatin 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 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-20093 Major surgery within 4 weeks prior to the first scheduled dose of HS-20093

* Subjects with previous or concurrent malignancies
* Inadequate bone marrow reserve or organ dysfunction
* Evidence of cardiovascular risk
* Evidence of current severe or uncontrolled systemic diseases
* Evidence of mucosal or internal bleeding within 1 month prior to the first scheduled dose of HS-20093
* Known active infection requiring antibodies treatment within 2 weeks, or severe infection within 4 weeks prior to the first scheduled dose of HS-20093
* Subjects with current infectious diseases
* History of neuropathy or mental disorders
* Pregnant or lactating female
* History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to HS-20093 or any of the components of HS-20093
* Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator
* Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments

Primary outcomes:
measure: Maximum tolerated dose (MTD) for combination-treatments
timeFrame: Up to day 21 from the first dose
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs)
timeFrame: From the first dose through 90 days post end of treatment
measure: Objective response rate (ORR) determined by investigators
timeFrame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
measure: Disease control rate (DCR) determined by investigators
timeFrame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
measure: Duration of response (DoR) determined by investigators
timeFrame: From the first dose up to PD or death, whichever came first, assessed up to 24 months
measure: Progression-free survival (PFS) determined by investigators according to RECIST 1.1
timeFrame: From the first dose up to PD or death, whichever came first, assessed up to 24 months
measure: Overall survival (OS)
timeFrame: From the first dose up to death, whichever came first, assessed up to 24 months
measure: Radiographic progression-free survival (rPFS) determined by investigators according to RECIST 1.1 and PCWG3
timeFrame: From the first dose up to PD or death from study, whichever came first, assessed up to 24 months
measure: Time to PSA progression (TTPP)
timeFrame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
measure: Prostate-specific cancer antigen (PSA) response rate
timeFrame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
measure: Time to first subsequent therapy (TFST)
timeFrame: From the first dose up to the imitation of subsequent therapy or death, whichever came first, assessed up to 24 months
measure: Observed maximum plasma concentration (Cmax) of HS-20093advanced solid tumor
timeFrame: From pre-dose to study completion, assessed up to 24 months
measure: Time to reach maximum plasma concentration (Tmax) of HS-20093
timeFrame: From pre-dose to study completion, assessed up to 24 months
measure: Terminal half-life (T1/2) of HS-20093 following the first dose
timeFrame: From pre-dose to study completion, assessed up to 24 months
measure: Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093
timeFrame: From pre-dose to study completion, assessed up to 24 months
measure: Percentage of participants with antibodies to HS-20093 in serum
timeFrame: From pre-dose to study completion, assessed up to 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
References: