Clinical trial NCT03913741: A Trial of Tisotumab Vedotin in Japanese Subjects With Advanced Solid Malignancies
Official title: Open Label Phase 1/2 Trial of Tisotumab Vedotin in Japanese Subjects With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: tisotumab vedotin
cervical cancer
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2019-04-12
Enrollment: 23
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group assignment
Primary purpose: TREATMENT

Brief summary: Open Label Phase 1/2 Trial of Tisotumab Vedotin in Japanese Subjects with Advanced Solid Malignancies

Detailed description: Part 1 of this trial will determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) and the safety profile of tisotumab vedotin in subjects with solid malignancies. Part 2 of this trial will enroll subjects with cervical cancer to provide further data on the safety, tolerability, PK and anti-tumor activity

Eligibility criteria: Inclusion Criteria (Main):

* PART 1 ONLY: Subjects with locally advanced or metastatic solid tumors, who have experienced disease progression while on standard therapy or are intolerant of, or not eligible for, standard therapy.
* PART 2 ONLY: Subjects with extra-pelvic metastatic or recurrent cervical cancer including squamous cell, adenocarcinoma or adenosquamous histology who have experienced disease progressed on standard of care chemotherapy in combination with bevacizumab, if eligible.

Patients must not have received more than 2 prior systemic treatment regimens for recurrent or metastatic cervical disease.

* Measurable disease according to RECIST v1.1
* Must be at least 20 years of age on the day of signing informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration
* Women of childbearing potential must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration
* A man who is sexually active with a WOCBP and has not had a vasectomy must agree to use a barrier method of birth control (Part 1 only)
* Must provide signed informed consent before any trial-related activity is carried out.

Exclusion Criteria (Main):

* PART 2 ONLY: Clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage.
* Known past or current coagulation defects leading to an increased risk of bleeding.
* Ongoing major bleeding.
* Has an active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible

Primary outcomes:
measure: Dose Escalation and Dose Expansion: Incidence of drug-related Adverse Events (AEs) and Serious Adverse Events (SAEs) by CTCAE v5.0 [Safety]
timeFrame: Throughout the trial - until 90 days after last dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion: Incidence of Dose Limiting Toxicities (DLTs), AEs, SAEs, adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [Tolerability]
timeFrame: Throughout the trial - until 90 days after last dose of tisotumab vedotin
measure: Dose Escalation: maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of tisotumab vedotin
timeFrame: Up to 21 days after the first dose of tisotumab vedotin (each cycle is 21 days)
measure: Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Maximum concentration (Cmax) after dosing
timeFrame: Up to approximately 42 days after initial dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC(0-t))
timeFrame: Up to approximately 42 days after initial dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin : Rate at which the drug is removed from the body (CL)
timeFrame: Up to approximately 42 days after initial dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Elimination half-life of the drug (T½)
timeFrame: Up to approximately 42 days after initial dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Time after dosing at which the maximum drug concentration was observed (Tmax)
timeFrame: Up to approximately 42 days after initial dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion: Assess immunogenicity of tisotumab vedotin by measuring and assessing Anti-drug Antibody (ADA)
timeFrame: Throughout and at the end of trial (up to 90 days after last dose of tisotumab vedotin)
Secondary outcomes:
measure: Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Objective Response Rate (ORR) (based on RECIST 1.1)
timeFrame: Up to approximately 6 months after the first dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Duration of Response (DOR) (based on RECIST 1.1)
timeFrame: Up to approximately 6 months after the first dose of tisotumab vedotin
measure: Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Time to Response (TTR) (based on RECIST 1.1)
timeFrame: Up to approximately 6 months after the first dose of tisotumab vedotin
Other outcomes:
Locations:
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hosptial East
state: Chiba-Ken
city: Matsuyama-Shi
country: Japan
facility: NHO Shikoku Cancer Center
state: Ehime-Ken
city: Sapporo-shi
country: Japan
facility: NHO Hokkaido Cancer Center
state: Hokkaido
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa-Ken
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama-Ken
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka-Ken
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo-To
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo-To
Study officials:
affiliation: Saitama Medical University International Medical Center
name: Keiichi Fujiwara, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yonemori K, Kuboki Y, Hasegawa K, Iwata T, Kato H, Takehara K, Hirashima Y, Kato H, Passey C, Buchbjerg JK, Harris JR, Andreassen CM, Nicacio L, Soumaoro I, Fujiwara K. Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study. Cancer Sci. 2022 Aug;113(8):2788-2797. doi: 10.1111/cas.15443. Epub 2022 Jun 15.