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ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas

Primary Purpose

Osteosarcoma, Sarcoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
HS-20093
Sponsored by
Hansoh BioMedical R&D Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: At least age of 18 years at screening; Patients with histologically confirmed relapsed or refractory osteosarcoma or other sarcomas who have progressed upon first-line systemic treatment. At least one measurable lesion according to RECIST 1.1. Agree to provide fresh or archival tumor tissue and peripheral blood samples. 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: 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 of the first dose of HS-20093. Spinal cord compression or brain metastases. Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 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. 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. History of other primary malignancies. Inadequate bone marrow reserve or organ dysfunction Evidence of cardiovascular risk. Severe, uncontrolled or active cardiovascular diseases. 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. Severe or poorly controlled hypertension. Bleeding symptoms with apparent clinical significance or obvious bleeding tendency within 1 months prior to the first dose of HS-20093 Serious arteriovenous thrombosis events occurred within 3 months before the first dose. Severe infections occurred within 4 weeks before the first dose. 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 The presence of active infectious diseases has been known before the first dose such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus HIV infection, etc. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis. Other moderate or severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity or may seriously affect respiratory function. Previous history of serious neurological or mental disorders, including epilepsy, dementia or severe depression and any other status that may interfere in assessment. Women who are breastfeeding or pregnant or planned to be pregnant during the study period. Vaccination or hypersensitivity of any level within 4 weeks prior to the first dose of HS-20093 History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins. Hypersensitivity to any ingredient 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

Sites / Locations

  • Wei GuoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

cohort 1 at HS-20093 8mg/kg (Phase 2a)

cohort 1 at HS-20093 12mg/kg (Phase 2a)

cohort 2 at HS-20093 12mg/kg (Phase 2a)

HS-20093(Phase 2b)

Arm Description

Participants in cohort 1 will be randomized to receive HS-20093 at 8 mg/kg.

Participants in cohort 1 will be randomized to receive HS-20093 at 12 mg/kg.

Participants in cohort 2 will receive HS-20093 at 12 mg/kg.

Participants will receive HS-20093 at the recommended dose from Phase 2a.

Outcomes

Primary Outcome Measures

Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].

Secondary Outcome Measures

Incidence and severity of adverse events (AEs)
AE assessed by investigator exclusively related to subject's underlying disease or medical condition [graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0]. Any untoward medical occurrence in a clinical study participant, whether or not considered related to the medicinal product. Incidence and severity of AEs are assessed according to vital signs, laboratory variables, physical examination, electrocardiogram, etc.
Observed maximum plasma concentration (Cmax) of HS-20093
Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose
Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Terminal half-life (T1/2) of HS-20093 following the first dose
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093
Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Percentage of participants with antibodies to HS-20093 in serum
Serum samples were collected for the determination of anti-drug antibody (ADA) at designated time points.
ORR determined by Independent review committee (IRC) according to RECIST 1.1
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by IRC based on RECIST version 1.1[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].
Duration of response (DoR) determined by investigators and IRC according to RECIST 1.1
DoR was defined as the period from the first occurrence of CR or PR to progressive disease (PD) or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used [Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].
Disease control rate (DCR) determined by investigators and IRC according to RECIST 1.1.
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) [Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose].
Progression-free survival (PFS) determined by investigators and IRC according to RECIST 1.1
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). PFS was defined as the time from first dose or random assignment (if any) to PD or death from any cause.
4-month PFS rate determined by investigators and IRC according to RECIST 1.1
4-month PFS rate is defined as the percentage of patients whose disease is progression free at 4 months from the start of treatment.
Overall survival (OS)
OS was defined as the time from the first dose or random assignment (if any) to death from any cause.

Full Information

First Posted
April 3, 2023
Last Updated
July 19, 2023
Sponsor
Hansoh BioMedical R&D Company
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1. Study Identification

Unique Protocol Identification Number
NCT05830123
Brief Title
ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas
Official Title
ARTEMIS-002: A Phase 2, Multicenter, Open-label Study of Intravenous Administration of HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hansoh BioMedical R&D Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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. This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20093 as a monotherapy in patients with relapsed or refractory osteosarcoma and other sarcomas.
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 advanced osteosarcoma upon disease progression after standard treatment. Cohort 2: Patients with other unresectable bone and soft tissue sarcomas, if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. Subjects will be randomly assigned in a 1:1 ratio to 8.0 mg/kg and 12.0 mg/kg of HS-20093 in cohort 1 and will receive 12.0 mg/kg in cohort 2. Phase 2b: The study will be conducted in patients with advanced osteosarcoma upon disease progression after standard treatment. Subjects will receive HS-20093 at the recommended dose from Phase 2a. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma, Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cohort 1 at HS-20093 8mg/kg (Phase 2a)
Arm Type
Experimental
Arm Description
Participants in cohort 1 will be randomized to receive HS-20093 at 8 mg/kg.
Arm Title
cohort 1 at HS-20093 12mg/kg (Phase 2a)
Arm Type
Experimental
Arm Description
Participants in cohort 1 will be randomized to receive HS-20093 at 12 mg/kg.
Arm Title
cohort 2 at HS-20093 12mg/kg (Phase 2a)
Arm Type
Experimental
Arm Description
Participants in cohort 2 will receive HS-20093 at 12 mg/kg.
Arm Title
HS-20093(Phase 2b)
Arm Type
Experimental
Arm Description
Participants will receive HS-20093 at the recommended dose from Phase 2a.
Intervention Type
Drug
Intervention Name(s)
HS-20093
Intervention Description
IV administration of HS-20093 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.
Primary Outcome Measure Information:
Title
Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Description
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].
Time Frame
From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Secondary Outcome Measure Information:
Title
Incidence and severity of adverse events (AEs)
Description
AE assessed by investigator exclusively related to subject's underlying disease or medical condition [graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0]. Any untoward medical occurrence in a clinical study participant, whether or not considered related to the medicinal product. Incidence and severity of AEs are assessed according to vital signs, laboratory variables, physical examination, electrocardiogram, etc.
Time Frame
From the first dose through 90 days post end of treatment.
Title
Observed maximum plasma concentration (Cmax) of HS-20093
Description
Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Time Frame
From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Title
Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose
Description
Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Time Frame
From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Title
Terminal half-life (T1/2) of HS-20093 following the first dose
Description
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Time Frame
From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Title
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093
Description
Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Time Frame
From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Title
Percentage of participants with antibodies to HS-20093 in serum
Description
Serum samples were collected for the determination of anti-drug antibody (ADA) at designated time points.
Time Frame
From pre-dose to 90 days post end of treatment
Title
ORR determined by Independent review committee (IRC) according to RECIST 1.1
Description
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by IRC based on RECIST version 1.1[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].
Time Frame
From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Title
Duration of response (DoR) determined by investigators and IRC according to RECIST 1.1
Description
DoR was defined as the period from the first occurrence of CR or PR to progressive disease (PD) or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used [Confirmed CR/PR assessment require at least one repeat (≥4 weeks)].
Time Frame
From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Title
Disease control rate (DCR) determined by investigators and IRC according to RECIST 1.1.
Description
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) [Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose].
Time Frame
From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Title
Progression-free survival (PFS) determined by investigators and IRC according to RECIST 1.1
Description
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). PFS was defined as the time from first dose or random assignment (if any) to PD or death from any cause.
Time Frame
From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Title
4-month PFS rate determined by investigators and IRC according to RECIST 1.1
Description
4-month PFS rate is defined as the percentage of patients whose disease is progression free at 4 months from the start of treatment.
Time Frame
4 months.
Title
Overall survival (OS)
Description
OS was defined as the time from the first dose or random assignment (if any) to death from any cause.
Time Frame
From the first dose or random assignment up to death or withdrawal from study, whichever came first, assessed up to 24 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: At least age of 18 years at screening; Patients with histologically confirmed relapsed or refractory osteosarcoma or other sarcomas who have progressed upon first-line systemic treatment. At least one measurable lesion according to RECIST 1.1. Agree to provide fresh or archival tumor tissue and peripheral blood samples. 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: 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 of the first dose of HS-20093. Spinal cord compression or brain metastases. Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 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. 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. History of other primary malignancies. Inadequate bone marrow reserve or organ dysfunction Evidence of cardiovascular risk. Severe, uncontrolled or active cardiovascular diseases. 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. Severe or poorly controlled hypertension. Bleeding symptoms with apparent clinical significance or obvious bleeding tendency within 1 months prior to the first dose of HS-20093 Serious arteriovenous thrombosis events occurred within 3 months before the first dose. Severe infections occurred within 4 weeks before the first dose. 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 The presence of active infectious diseases has been known before the first dose such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus HIV infection, etc. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis. Other moderate or severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity or may seriously affect respiratory function. Previous history of serious neurological or mental disorders, including epilepsy, dementia or severe depression and any other status that may interfere in assessment. Women who are breastfeeding or pregnant or planned to be pregnant during the study period. Vaccination or hypersensitivity of any level within 4 weeks prior to the first dose of HS-20093 History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins. Hypersensitivity to any ingredient 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Guo, MD
Phone
010-88326656
Email
bonetumor@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Cuicui Cong
Phone
01088324516
Email
rmyyllwyh@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Guo, MD
Organizational Affiliation
Peking University People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Guowen Wang
Organizational Affiliation
Tianjin Medical University Cancer Institute and Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haiyan Hu
Organizational Affiliation
Shanghai 6th People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yingqi Hua
Organizational Affiliation
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jingnan Shen
Organizational Affiliation
First Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xing Zhang
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
jin Wang
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jing Chen
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Weitao Yao
Organizational Affiliation
Henan Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhaoming Ye
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wei Guo
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Guo, MD
Phone
01088326656
Email
bonetumor@163.com
First Name & Middle Initial & Last Name & Degree
Cuicui Cong
Phone
01088324516
Email
rmyyllwyh@163.com

12. IPD Sharing Statement

Learn more about this trial

ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas

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