Phase 1 First-in-human Study of JS014
Primary Purpose
Neoplasm Malignant, Neoplasm, Experimental, Solid Tumor, Adult
Status
Recruiting
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
JS014, Interleukin 21 and humanized anti-human serum albumin VHH antibody
Pembrolizumab - anti-PD-1 antibody
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasm Malignant focused on measuring phase 1, JS014, first-in-human
Eligibility Criteria
Inclusion Criteria:
- Older 18 years of age or per local regulation
- Subjects with advanced cancer or lymphoma who have no standard therapy available, ineligible for standard therapy or unwilling to receive cytotoxic therapy .
- ECOG PS 0-1
- A life expectancy longer than three months
- Adequate organ functions
- Able to adopt effective contraceptive measures
Exclusion Criteria:
- Known history of allergies to JS014 or IL-21 or human serum albumin or pembrolizumab (Ib only)
- Subjects who have received major surgery less than 4 weeks before 1st infusion of JS014
- Subjects who has a history of immune-related adverse events in prior immunotherapy.
- Subjects who have received immunosuppressive therapy less than 4 weeks before 1st infusion of JS014.
- Subjects who have two or more primary cancers in the past 5 years.
- Newly diagnosed or symptomatic brain metastases.
- Subjects who have received prior anti-cancer therapy with residual toxicities greater than grade 2.
- Subjects who have a history of autoimmune disease in 2 years.
- Subjects who have active infection, or uncontrollable hypertension, unstable angina, active peptic ulcer, recent acute myocardial infarction, severe congestive heart failure, or unhealed wound.
- Subjects with active hepatitis B or hepatitis C.
- Subjects who are pregnant or breast feeding.
- Subjects who primary immune deficiency.
Sites / Locations
- Taipei Medical University -Shuang Ho HospitalRecruiting
- Wanfang Hospital -Taipei Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Dose escalation
Arm Description
A open-label single arm of JS014 alone or in combination with pembrolizumab
Outcomes
Primary Outcome Measures
The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0
To determine the percentage of various toxicities assessed by CTCAE at different dose levels alone or in combination with pembrolizumab
Maximum tolerated dose (MTD) of JS014
To determine the MTD of JS014 alone or in combination with pembrolizumab
Recommended phase-2 dose (RP2D) of JS014
To determine of the RP2D of JS014 alone or in combination of pembrolizumab
Secondary Outcome Measures
Area under the curve (AUC) of JS014
To estimate the AUC of JS014 at different dose levels alone or in combination with pembrolizumab
Maximum concentration (Cmax) of JS014
To measure the Cmax after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Clearance of JS014
To estimate the clearance of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Half life (T1/2) of JS014
To estimate the T1/2 at terminal phase of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Volume of distribution (Vd) of JS014
To estimate Vd of JS014 after 1st and repeat dose alone or in combination with pembrolizumab
Time to reach maximum concentration (Tmax) of JS014
To estimate Tmax of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Overall response rate (ORR) alone or in combination with pembrolizumab
The assess the ORR of JS014 alone or in combination with pembrolizumab at different dose levels
Duration of response (DoR) alone or in combination with pembrolizumab
To estimate the DoR at different dose levels alone or in combination with pembrolizumab
Prevalence of anti-JS014 antibody
To estimate prevalence of anti-JS014 antibody at different dose levels alone or in combination with pembrolizumab
Titers of anti-JS014 antibody
To measure the titer of anti-JS014 antibody alone or in combination with pembrolizumab at different dose levels during the study
Full Information
NCT ID
NCT05296772
First Posted
February 28, 2022
Last Updated
September 3, 2023
Sponsor
Anwita Biosciences
Collaborators
Shanghai Junshi Bioscience Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05296772
Brief Title
Phase 1 First-in-human Study of JS014
Official Title
A Phase 1 Study of JS014, a Recombinant Fusion Protein of Interleukin-21 and Humanized Anti-human Serum Albumin VHH Antibody as a Single Agent or in Combination With Pembrolizumab in Subjects With Advanced Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Anwita Biosciences
Collaborators
Shanghai Junshi Bioscience Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase 1, first-in-human study uses a BOIN design to assess the safety and potential efficacy of JS014 at different dose levels as a single agent and in combination with fixed dose of pembrolizumab in subjects with advanced cancer.
Detailed Description
This study has two parts: 1a and Ib. Ia is a single agent study, and Ib is a combination study, testing the safety of JS014 with 200 mg of pembrolizumab. After being informed about the study and the potential risks, all subjects giving written informed consent will receive at most 4-week screening procedures to ensure the eligibility of the study entry. Once eligible, the subjects will receive JS014 infusion at the designated dose levels once every week until disease progression. In Ia study, only JS014 is given. In Ib study, JS014 will be given once a week with pembrolizumab at 200 mg once every three weeks until disease progression. The subjects will receive safety evaluation, pharmacokinetic and pharmacodynamic studies, as well as efficacy evaluation at regular interval.
The maximum number in each part of the study is 30 subjects. The Ia study will be conducted in Taiwan, and Ib study will be conducted in both Taiwan and the United States.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm Malignant, Neoplasm, Experimental, Solid Tumor, Adult, Lymphoma
Keywords
phase 1, JS014, first-in-human
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Single group assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose escalation
Arm Type
Other
Arm Description
A open-label single arm of JS014 alone or in combination with pembrolizumab
Intervention Type
Biological
Intervention Name(s)
JS014, Interleukin 21 and humanized anti-human serum albumin VHH antibody
Intervention Description
Weekly infusion at the designated dose level until disease progression, withdrawal or up to two years
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab - anti-PD-1 antibody
Other Intervention Name(s)
Keytruda
Intervention Description
200 mg, once every three weeks until disease progression, withdrawal or up to two years
Primary Outcome Measure Information:
Title
The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0
Description
To determine the percentage of various toxicities assessed by CTCAE at different dose levels alone or in combination with pembrolizumab
Time Frame
24 months
Title
Maximum tolerated dose (MTD) of JS014
Description
To determine the MTD of JS014 alone or in combination with pembrolizumab
Time Frame
24 months
Title
Recommended phase-2 dose (RP2D) of JS014
Description
To determine of the RP2D of JS014 alone or in combination of pembrolizumab
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Area under the curve (AUC) of JS014
Description
To estimate the AUC of JS014 at different dose levels alone or in combination with pembrolizumab
Time Frame
24 months
Title
Maximum concentration (Cmax) of JS014
Description
To measure the Cmax after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Time Frame
24 months
Title
Clearance of JS014
Description
To estimate the clearance of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Time Frame
24 months
Title
Half life (T1/2) of JS014
Description
To estimate the T1/2 at terminal phase of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Time Frame
24 months
Title
Volume of distribution (Vd) of JS014
Description
To estimate Vd of JS014 after 1st and repeat dose alone or in combination with pembrolizumab
Time Frame
24 months
Title
Time to reach maximum concentration (Tmax) of JS014
Description
To estimate Tmax of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Time Frame
24 months
Title
Overall response rate (ORR) alone or in combination with pembrolizumab
Description
The assess the ORR of JS014 alone or in combination with pembrolizumab at different dose levels
Time Frame
24 months
Title
Duration of response (DoR) alone or in combination with pembrolizumab
Description
To estimate the DoR at different dose levels alone or in combination with pembrolizumab
Time Frame
24 months
Title
Prevalence of anti-JS014 antibody
Description
To estimate prevalence of anti-JS014 antibody at different dose levels alone or in combination with pembrolizumab
Time Frame
24 months
Title
Titers of anti-JS014 antibody
Description
To measure the titer of anti-JS014 antibody alone or in combination with pembrolizumab at different dose levels during the study
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Older 18 years of age or per local regulation
Subjects with advanced cancer or lymphoma who have no standard therapy available, ineligible for standard therapy or unwilling to receive cytotoxic therapy .
ECOG PS 0-1
A life expectancy longer than three months
Adequate organ functions
Able to adopt effective contraceptive measures
Exclusion Criteria:
Known history of allergies to JS014 or IL-21 or human serum albumin or pembrolizumab (Ib only)
Subjects who have received major surgery less than 4 weeks before 1st infusion of JS014
Subjects who has a history of immune-related adverse events in prior immunotherapy.
Subjects who have received immunosuppressive therapy less than 4 weeks before 1st infusion of JS014.
Subjects who have two or more primary cancers in the past 5 years.
Newly diagnosed or symptomatic brain metastases.
Subjects who have received prior anti-cancer therapy with residual toxicities greater than grade 2.
Subjects who have a history of autoimmune disease in 2 years.
Subjects who have active infection, or uncontrollable hypertension, unstable angina, active peptic ulcer, recent acute myocardial infarction, severe congestive heart failure, or unhealed wound.
Subjects with active hepatitis B or hepatitis C.
Subjects who are pregnant or breast feeding.
Subjects who primary immune deficiency.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
E Liu, MD
Phone
(650)660-9828
Email
eliu@anwitabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
TJ Chiou, MD
Organizational Affiliation
Wanfang Hospital-Taipei Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Taipei Medical University -Shuang Ho Hospital
City
New Taipei City
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracy Chui
Email
tchui@zuelligpharma.com
First Name & Middle Initial & Last Name & Degree
Po-Ya Chuang, MD
Facility Name
Wanfang Hospital -Taipei Medical University
City
Taipei
ZIP/Postal Code
106
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
HY Wang
Phone
886-29307930
Ext
2543
Email
109093@w.tmu.edu.tw
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 1 First-in-human Study of JS014
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