Clinical trial NCT05296772: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasm Malignant
Neoplasm, Experimental
Solid Tumor, Adult
Lymphoma
Keywords: phase 1
JS014
first-in-human
Lead sponsor: Anwita Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Junshi Bioscience Co., Ltd.
First posted: 2022-03-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Single group assignment
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The numbers of participants with treatment-related adverse events assessed by CTCAE 5.0
timeFrame: 24 months
measure: Maximum tolerated dose (MTD) of JS014
timeFrame: 24 months
measure: Recommended phase-2 dose (RP2D) of JS014
timeFrame: 24 months
Secondary outcomes:
measure: Area under the curve (AUC) of JS014
timeFrame: 24 months
measure: Maximum concentration (Cmax) of JS014
timeFrame: 24 months
measure: Clearance of JS014
timeFrame: 24 months
measure: Half life (T1/2) of JS014
timeFrame: 24 months
measure: Volume of distribution (Vd) of JS014
timeFrame: 24 months
measure: Time to reach maximum concentration (Tmax) of JS014
timeFrame: 24 months
measure: Overall response rate (ORR) alone or in combination with pembrolizumab
timeFrame: 24 months
measure: Duration of response (DoR) alone or in combination with pembrolizumab
timeFrame: 24 months
measure: Prevalence of anti-JS014 antibody
timeFrame: 24 months
measure: Titers of anti-JS014 antibody
timeFrame: 24 months
Other outcomes:
Locations:
city: New Taipei City
country: Taiwan
facility: Taipei Medical University -Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Wanfang Hospital -Taipei Medical University
Study officials:
affiliation: Wanfang Hospital-Taipei Medical University
name: TJ Chiou, MD
role: PRINCIPAL_INVESTIGATOR
References: