To Evaluate Pharmacokinetics of Tisotumab Vedotin in Chinese Subjects With Metastatic or Recurrent Solid Malignancies

NCT ID: NCT05866354

Last Updated: 2023-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-16

Study Completion Date

2023-11-02

Brief Summary

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The goal of this clinical trial is to test in Chinese Subjects with Metastatic or Recurrent Solid Malignancies. The main questions it aims to answer are:

* How is the PK of tisotumab vedotin?
* How is the immunogenicity of tisotumab vedotin?
* How is the safety and tolerability of tisotumab vedotin?
* How is the clinical efficacy of tisotumab vedotin? Participants will receive 2.0 mg/kg tisotumab vedotin (up to a maximum of 200 mg in subjects ≥ 100 kg) as a 30-minute IV infusion 1Q3W with the aim to characterize the PK profiles and to evaluate immunogenicity, safety, and tolerability of tisotumab vedotin in the Chinese population.

Subjects will receive study treatment until disease progression or any other discontinuation criteria are met, whichever occurs first. Subjects will undergo an end of treatment (EOT) visit 30 days (± 5 days) after the last dose of study treatment or within 7 days after treatment discontinuation has been decided, whichever occurs later.

Detailed Description

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This is an open-label, phase 1, PK trial of intravenous tisotumab vedotin in Chinese subjects with recurrent or metastatic solid tumors who have failed on previous standard systemic therapy. The screening period will be up to 28 days, after which eligible subjects will receive 2.0 mg/kg tisotumab vedotin (up to a maximum of 200 mg in subjects ≥ 100 kg) as a 30-minute IV infusion 1Q3W with the aim to characterize the PK profiles and to evaluate immunogenicity, safety, and tolerability of tisotumab vedotin in the Chinese population.

Subjects will receive study treatment until disease progression or any other discontinuation criteria are met, whichever occurs first. Subjects will undergo an end of treatment (EOT) visit 30 days (± 5 days) after the last dose of study treatment or within 7 days after treatment discontinuation has been decided, whichever occurs later.

Blood samples for the assessment of tisotumab vedotin concentrations and antidrug antibody (ADA) will be drawn in accordance with the PK and ADA collection schedule. Three different PK analytes will be measured: 1) tisotumab vedotin (conjugated antibody only), 2) total antibody (ie, conjugated and unconjugated antibody), and 3) free MMAE. PK parameters to be estimated will include, but are not limited to, AUC, Cmax, time to maximum concentration (Tmax), apparent terminal half-life (t1/2), and trough concentration (Ctrough).

Safety and tolerability will be evaluated based on TEAEs, clinical safety assessments and clinical laboratory assessments. Ocular AEs are a known safety risk of tisotumab vedotin treatment. Therefore, the eye care plan will be implemented for all subjects enrolled in this trial.

Efficacy assessments will include confirmed ORR assessed by the investigator, primarily based on the enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans performed at protocol-specified time points. The RECIST v1.1 criteria will be used for response evaluation. After discontinuation of study treatment, tumor assessments may or may not be performed at the discretion of the investigator.

At the end of study (EOS), sponsor will ensure provision of continued tisotumab vedotin to subjects with clinical benefit defined as stable disease (SD) or better, until criteria of treatment discontinuation are met.

Conditions

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Solid Malignancies

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Tisotumab Vedotin

Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue factor (TF), a protein aberrantly expressed in a wide number of solid tumors including cervical cancer.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years.
2. Must sign an informed consent form (ICF) .
3. Must have recurrent or metastatic solid tumors and have failed on previous standard systemic therapy.
4. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Has life expectancy of at least 3 months.
6. Must demonstrate acceptable screening laboratory values.
7. Female subjects must agree not to breastfeed or donate ova. A male subject who is sexually active with a female partner of reproductive potential and has not had a vasectomy must agree to use a barrier method of birth control (eg, condom with spermicide), and all men must also not donate sperm during the trial and for 6 months after receiving the last dose of tisotumab vedotin.
8. Any other toxicity caused by previous treatment should have recovered to ≤ CTCAE grade 1 or baseline level, except ≤ CTCAE grade 2 alopecia.

Exclusion Criteria

1. Has clinically significant bleeding issues or risks:
2. Has cardiovascular issues or risks:
3. Central nervous system (CNS): any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack \> 1 month prior to screening is allowed).
4. Ophthalmological: active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis (eg, Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), and subjects with penetrating ocular transplants are ineligible. Cataracts alone is not an exclusion criterion.
5. Surgery/procedures: major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration.
6. Peripheral neuropathy ≥ grade 2.
7. Any prior treatment with MMAE-derived drugs.
8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of tisotumab vedotin.
9. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zai Lab (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rutie Yin, Dr

Role: PRINCIPAL_INVESTIGATOR

West China Second University Hospital

Guiling Li, Dr

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Bingzhong Zhang, Dr

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Qing Wen, Dr

Role: PRINCIPAL_INVESTIGATOR

Jinan Central Hospital

Meili Sun, Dr

Role: PRINCIPAL_INVESTIGATOR

Jinan Central Hospital

Jianhua Shi, Dr

Role: PRINCIPAL_INVESTIGATOR

Linyi Cancer Hospital

Dongqing Lv, Dr

Role: PRINCIPAL_INVESTIGATOR

Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

Tienan Yi, Dr

Role: PRINCIPAL_INVESTIGATOR

Xiangyang Central Hospital

Locations

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Jinan Central Hospital

Jinan, Shangdong, China

Site Status

Countries

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China

Other Identifiers

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ZL-1309-002

Identifier Type: -

Identifier Source: org_study_id