Phase 1 First-in-human Study of JS014

Phase 1

Recruiting

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

• Registration Number: NCT05296772
• Lead Sponsor: Anwita Biosciences

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.

Study Timeline

• Study Start: 2022-02-28
• Study First Submitted: 2022-02-28
• Study First Submitted QC: 2022-03-16
• Study First Posted: 2022-03-25
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-03
• Last Update Posted: 2023-09-06
• Primary Completion: 2024-06
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation	JS014, Interleukin 21 and humanized anti-human serum albumin VHH antibody	A open-label single arm of JS014 alone or in combination with pembrolizumab
Dose escalation	Pembrolizumab - anti-PD-1 antibody	A open-label single arm of JS014 alone or in combination with pembrolizumab

Primary Outcome Measures

Name	Time	Method
The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0	24 months	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	24 months	To determine the MTD of JS014 alone or in combination with pembrolizumab
Recommended phase-2 dose (RP2D) of JS014	24 months	To determine of the RP2D of JS014 alone or in combination of pembrolizumab

Secondary Outcome Measures

Name	Time	Method
Area under the curve (AUC) of JS014	24 months	To estimate the AUC of JS014 at different dose levels alone or in combination with pembrolizumab
Maximum concentration (Cmax) of JS014	24 months	To measure the Cmax after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Time to reach maximum concentration (Tmax) of JS014	24 months	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	24 months	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	24 months	To estimate the DoR at different dose levels alone or in combination with pembrolizumab
Half life (T1/2) of JS014	24 months	To estimate the T1/2 at terminal phase of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Titers of anti-JS014 antibody	24 months	To measure the titer of anti-JS014 antibody alone or in combination with pembrolizumab at different dose levels during the study
Clearance of JS014	24 months	To estimate the clearance of JS014 after 1st and repeat dose of JS014 alone or in combination with pembrolizumab
Volume of distribution (Vd) of JS014	24 months	To estimate Vd of JS014 after 1st and repeat dose alone or in combination with pembrolizumab
Prevalence of anti-JS014 antibody	24 months	To estimate prevalence of anti-JS014 antibody at different dose levels alone or in combination with pembrolizumab

Trial Locations

Locations (2)

Taipei Medical University -Shuang Ho Hospital; 🇨🇳 New Taipei City, Taiwan

Wanfang Hospital -Taipei Medical University; 🇨🇳 Taipei, Taiwan