Clinical trial NCT06001255: ARTEMIS-003: HS-20093 in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC) and Advanced Solid Tumors
Official title: ARTEMIS-003: A Phase 2, Open-label, Multi-center Study to Evaluate Efficacy, Safety, and Pharmacokinetics, of Intravenous Administration of HS-20093 in Patients With Metastasis Castration Resistant Prostate Cancer and Advanced Solid Tumors Who Have Progressed Following at Least One Prior Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastasis Castration Resistant Prostate Cancer(mCRPC)
Lead sponsor: Hansoh BioMedical R&D Company
Sponsor class: INDUSTRY
First posted: 2023-08-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 anti-tumor activity, safety and pharmacokinetics of HS-20093 in Chinese patients with metastasis Castration Resistant Prostate Cancer.

This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, tolerability and pharmacokinetic (PK) of HS-20093 as a monotherapy in subjects with metastasis castration resistant prostate cancers (mCRPC) and other solid tumors.

Detailed description: This is a phase 2, open-label, multi-center study consisting of two parts: Phase 2a and 2b.

Phase 2a: The study will be conducted in the following two cohorts: Cohort 1: Patients with metastasis castration resistant prostate cancers who have progressed on or intolerant to standard therapies. Cohort 2: Other patients with advanced solid tumor if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. All subjects will receive 8 mg/kg of HS-20093.

Phase 2b: The study will be conducted in patients with metastasis castration resistant prostate cancers who have progressed on or intolerant to standard therapies. Subjects will receive 8 mg/kg of HS-20093.

All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of HS-20093. 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:

* Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. Men or women greater than or equal to 18 years.
  2. Locally advanced or metastatic solid tumors confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable.
  3. At least one measurable lesion in accordance with RECIST 1.1.
  4. Agree to provide fresh archival tumor tissue.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1.
  6. Estimated life expectancy ≥ 12 weeks.
  7. Men or women should be using adequate contraceptive measures throughout the study.
  8. Female subjects must not be pregnant at screening or have evidence of non-childbearing potential.
  9. Signed and dated Informed Consent Form.

Exclusion Criteria:

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

  1. Treatment with any of the following:

     Previous or current treatment with B7-H3 targeted therapy. Any 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.

     Pleural or peritoneal effusion requiring clinical intervention. Pericardial effusion.

     Major surgery within 4 weeks prior to the first scheduled dose of HS-20093. Spinal cord compression or brain metastases. Treatment with drugs that are predominantly strong inhibitors or inducers or sensitive substrates of CYP3A4, CYP2D6, P-gp or BCRP with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study.

     Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study
  2. Patients with BRCA and ATM mutation.
  3. Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 with the exception of alopecia or neurotoxicity
  4. History of other primary malignancies.
  5. Inadequate bone marrow reserve or organ dysfunction.
  6. Evidence of cardiovascular risk.
  7. Severe, uncontrolled or active cardiovascular diseases.
  8. Severe or uncontrolled diabetes, including diabetes ketoacidosis or hyperglycemia hypertonic occurring within 6 months before the first dose of the study drug, or the glycosylated hemoglobin value ≥ 7.5% in the screening period.
  9. Severe or poorly controlled hypertension.
  10. Bleeding symptoms with apparent clinical significance or obvious bleeding tendency within 1 months prior to the first dose of HS-20093
  11. Serious arteriovenous thrombosis events occurred within 3 months before the first dose
  12. Severe infections occurred within 4 weeks before the first dose
  13. Patients who have received continuous steroid treatment for more than 30 days within 30 days before the first dose, or need long-term (≥ 30 days) steroid treatment, or who have other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation
  14. The presence of active infectious diseases before the first dose such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus HIV infection, etc.
  15. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis
  16. Other moderate or severe urinary diseases that may interfere with the detection or treatment of drug-related urinary toxicity or may seriously affect urinary function.
  17. History of serious neuropathy or mental disorders.
  18. Women who are breastfeeding or pregnant or planned to be pregnant during the study period.
  19. Vaccination or hypersensitivity of any level within 4 weeks prior to the first dose of HS-20093
  20. History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins
  21. Hypersensitivity to any ingredient of HS-20093
  22. Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
  23. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

Primary outcomes:
measure: Objective response rate (ORR) determined by investigators
timeFrame: From the first dose up to disease progression or withdrawal from study, which ever came first, assessed up to 24 months
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs).
timeFrame: From the first dose through 90 days post end of treatment.
measure: Observed maximum plasma concentration (Cmax) of HS-20093.
timeFrame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
measure: Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose.
timeFrame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days).
measure: Terminal half-life (T1/2) of HS-20093 following the first dose.
timeFrame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days).
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 14 days after the first dose on Cycle 1 (each cycle is 21 days).
measure: Percentage of participants with antibodies to HS-20093 in serum
timeFrame: From pre-dose to 90 days post end of treatment.
measure: ORR determined by Independent review committee (IRC)
timeFrame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months
measure: Duration of response (DoR) determined by investigators and IRC according to RECIST 1.1 and PCWG3
timeFrame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months
measure: Disease control rate (DCR) determined by investigators and IRC according to RECIST 1.1 and PCWG3
timeFrame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months
measure: Progression-free survival (PFS) determined by investigators and IRC according to RECIST 1.1 and PCWG3
timeFrame: From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
measure: Radiographic Progression-Free Survival (rPFS) determined by investigators and IRC according to RECIST 1.1 and PCWG3
timeFrame: From the first dose or random assignment up to disease progression, assessed up to 24 months.
measure: Overall survival (OS)
timeFrame: From the first dose or random assignment up to death 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 or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
measure: Time to PSA progression
timeFrame: From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: West China hospital, sichuan university
city: Guangzhou
country: China
facility: The First Affiliate Hospital of GUANGZHOU Medical University
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanjing
country: China
facility: Affiliated Drum Tower Hospital, Medical School of Nanjing University
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Cancer Hospital
city: Shengyang
country: China
facility: Liaoning Tumor Hospital
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
city: Shengyang
country: China
facility: The First Hospital of China Medical University
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Tongji Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
References: