A Trial of Tisotumab Vedotin in Japanese Subjects With Advanced Solid Malignancies

Solid Tumor Clinical Trial

— innovaTV 206  

Official title:

Open Label Phase 1/2 Trial of Tisotumab Vedotin in Japanese Subjects With Advanced Solid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03913741
• Other study ID #: GCT1015-06
• Secondary ID: JapicCTI-194639
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 27, 2019
• Est. completion date: October 30, 2021

Study information

• Verified date: December 2021
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 30, 2021
• Est. primary completion date: August 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• tisotumab vedotin
Tisotumab vedotin will be administered intravenously once every 21 days. The dose levels will be determined by the starting dose and the escalation steps taken in the trial

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo-To
Japan	Saitama Medical University International Medical Center	Hidaka-shi	Saitama-Ken
Japan	National Cancer Center Hosptial East	Kashiwa-shi	Chiba-Ken
Japan	NHO Shikoku Cancer Center	Matsuyama-Shi	Ehime-Ken
Japan	NHO Hokkaido Cancer Center	Sapporo-shi	Hokkaido
Japan	Keio University Hospital	Shinjuku-ku	Tokyo-To
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka-Ken
Japan	Kanagawa Cancer Center	Yokohama-shi	Kanagawa-Ken

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	Seagen Inc.

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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: Resu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation and Dose Expansion: Incidence of drug-related Adverse Events (AEs) and Serious Adverse Events (SAEs) by CTCAE v5.0 [Safety]		Throughout the trial - until 90 days after last dose of tisotumab vedotin
Primary	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]		Throughout the trial - until 90 days after last dose of tisotumab vedotin
Primary	Dose Escalation: maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of tisotumab vedotin		Up to 21 days after the first dose of tisotumab vedotin (each cycle is 21 days)
Primary	Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Maximum concentration (Cmax) after dosing		Up to approximately 42 days after initial dose of tisotumab vedotin
Primary	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))		Up to approximately 42 days after initial dose of tisotumab vedotin
Primary	Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin : Rate at which the drug is removed from the body (CL)		Up to approximately 42 days after initial dose of tisotumab vedotin
Primary	Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Elimination half-life of the drug (T½)		Up to approximately 42 days after initial dose of tisotumab vedotin
Primary	Dose Escalation and Dose Expansion Pharmacokinetics of tisotumab vedotin: Time after dosing at which the maximum drug concentration was observed (Tmax)		Up to approximately 42 days after initial dose of tisotumab vedotin
Primary	Dose Escalation and Dose Expansion: Assess immunogenicity of tisotumab vedotin by measuring and assessing Anti-drug Antibody (ADA)	Summarized by descriptive statistics by trial part and dose	Throughout and at the end of trial (up to 90 days after last dose of tisotumab vedotin)
Secondary	Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Objective Response Rate (ORR) (based on RECIST 1.1)	ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR)	Up to approximately 6 months after the first dose of tisotumab vedotin
Secondary	Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Duration of Response (DOR) (based on RECIST 1.1)	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 6 months after the first dose of tisotumab vedotin
Secondary	Dose Escalation and Dose Expansion: Evaluate antitumor activity of tisotumab vedotin by assessing Time to Response (TTR) (based on RECIST 1.1)	TTR for a responder is defined as the time from the start of treatment with study drug to the first objective tumor response observed.	Up to approximately 6 months after the first dose of tisotumab vedotin