Phase 1 First-in-human Study of JS014

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Solid Tumor, Adult; Neoplasm Malignant; Neoplasm, Experimental
• Intervention / Treatment: Biological: JS014, Interleukin 21 and humanized anti-human serum albumin VHH antibody; Biological: Pembrolizumab - anti-PD-1 antibody

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: E Liu, MD; Phone Number: (650)660-9828; Email: eliu@anwitabio.com

Study Locations

• Taiwan
  • New Taipei City, Taiwan
    • Recruiting
    • Taipei Medical University -Shuang Ho Hospital
    • Contact: Tracy Chui; Email: tchui@zuelligpharma.com
    • Principal Investigator: Po-Ya Chuang, MD
  • Taipei, Taiwan, 106
    • Recruiting
    • Wanfang Hospital -Taipei Medical University
    • Contact: HY Wang; Phone Number: 2543 886-29307930; Email: 109093@w.tmu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dose escalation; A open-label single arm of JS014 alone or in combination with pembrolizumab	Biological: JS014, Interleukin 21 and humanized anti-human serum albumin VHH antibody; Weekly infusion at the designated dose level until disease progression, withdrawal or up to two years; Biological: Pembrolizumab - anti-PD-1 antibody; 200 mg, once every three weeks until disease progression, withdrawal or up to two years; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 months
Maximum tolerated dose (MTD) of JS014	To determine the MTD of JS014 alone or in combination with pembrolizumab	24 months
Recommended phase-2 dose (RP2D) of JS014	To determine of the RP2D of JS014 alone or in combination of pembrolizumab	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of JS014	To estimate the AUC of JS014 at different dose levels alone or in combination with pembrolizumab	24 months
Maximum concentration (Cmax) of JS014	To measure the Cmax after 1st and repeat dose of JS014 alone or in combination with pembrolizumab	24 months
Clearance of JS014	To estimate the clearance of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab	24 months
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	24 months
Volume of distribution (Vd) of JS014	To estimate Vd of JS014 after 1st and repeat dose alone or in combination with pembrolizumab	24 months
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	24 months
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	24 months
Duration of response (DoR) alone or in combination with pembrolizumab	To estimate the DoR at different dose levels alone or in combination with pembrolizumab	24 months
Prevalence of anti-JS014 antibody	To estimate prevalence of anti-JS014 antibody at different dose levels alone or in combination with pembrolizumab	24 months
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	24 months

Collaborators and Investigators

• Sponsor: Anwita Biosciences
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: TJ Chiou, MD, Wanfang Hospital-Taipei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: March 16, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 3, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: phase 1; first-in-human; JS014
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms, Experimental; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibodies; Immunoglobulins; Pembrolizumab
• Other Study ID Numbers: AWT-EXK21-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No