Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Tisotumab vedotin

Antineoplastic Agents, Immunological

tisotumab vedotin

Kristi Schmidt, MD

This trial will study tisotumab vedotin to find out what its side effects are and to see if it works for platinum-resistant ovarian cancer (PROC). It will test different doses of tisotumab vedotin that are given at different times. It will also compare the side effects and ability to treat tumors of these different doses and schedules. In this study, there will be a safety run-in group of approximately 12 patients that will look at a dose-dense treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In addition to the safety run-in patients, there will be three groups in the study. One group will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).

The study objectives are to evaluate the safety, antitumor activity, and pharmacokinetics of tisotumab vedotin (TV) administered every 3 weeks or on Days 1, 8, and 15 of every 4-week cycle (3Q4W) for patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has relapsed within 6 months of the completion of platinum-based treatment and determined to be platinum resistant. All patients must have PROC and be eligible for single agent chemotherapy.

The safety run-in period will evaluate the safety of a weekly schedule. The highest dose level that is considered safe will be the recommended phase 2 dose (RP2D) and will be used in Part A. In Part A, participants will be randomized in a 1:1 ratio to receive tisotumab vedotin intravenously (IV) every 3 weeks (Q3W regimen) or the safety run-in RP2D on Days 1, 8, and 15 of every 4-week cycle (weekly regimen; 3Q4W) if a RP2D has been identified. Participants who enroll in Part B will receive tisotumab vedotin on Days 1, 8, and 15 of every 4-week cycle (weekly regimen) at a pre-specified dose level, if the dose level is considered safe and tolerable in the safety run-in period.

A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)

Open Label Phase 2 Study of Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With a Safety Run-in of a Dose-Dense Regimen

Incidence of dose-limiting toxicity (DLT) was evaluated in participants enrolled in the Safety Run-In, who were followed for protocol-defined DLT events up to 28 days after the first dose of tisotumab vedotin.

Proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment.

Proportion of participants who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator

Percentage of participants who have at least a 50% reduction in CA-125 value from baseline

Percentage of participants whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria

Time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or death due to any cause, whichever comes first

Percentage of participants who achieved a confirmed Complete Response(CR) or Partial Response (PR) per RECIST v1.1 as assessed by the investigator, or meet the Stable Disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks.

Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)

Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first

Time from the start of study treatment to date of death due to any cause

The proportion of participants who develop ATA at any time during the study. A positive baseline ATA result is considered positive post-baseline if the post-baseline ATA titer result is at least four times higher than the baseline result.

ADC Cmax was derived from the PK blood samples collected.

ADC Tmax was derived from the PK blood samples collected.

ADC AUC was derived from the PK blood samples collected.

MMAE Cmax was derived from the PK blood samples collected.

MMAE Tmax was derived from the PK blood samples collected.

MMAE AUC was derived from the PK blood samples collected.

MMAE Ctrough was derived from the PK blood samples collected.

TAb Cmax was derived from the PK blood samples collected.

TAb Tmax was derived from the PK blood samples collected.

TAb AUC was derived from the PK blood samples collected.

Genmab

Seagen Inc.

All-cause mortality includes all participants that were enrolled in the study regardless of whether or not they received treatment. Non-serious AEs and SAEs were collected and reported for patients that received treatment in their respective arms.

Tisotumab Vedotin 0.9 mg/kg by IV infusion on Days 1, 8, and 15 of every 4-week cycle

Safety Run-In 0.9 mg/kg 3Q4W

Tisotumab Vedotin 1.2 mg/kg by IV infusion on Days 1, 8, and 15 of every 4-week cycle

Safety Run-In 1.2 mg/kg 3Q4W

Part B Expansion

Total

Age, Continuous

Sex/Gender, Customized

Race (NIH/OMB)

Race/Ethnicity, Customized

Measure Description: 0=Normal activity; 1=Symtoms but ambulatory; 2=In bed \<50% of the time; 3= In bed \> 50% of the time; 4=100% bedridden; 5=Dead

Eastern Cooperative Oncology Group (ECOG) Performance Score

The Safety Analysis Set includes all participants who received any amount of study drug.

Chief Medical Officer

Participants from the Safety Analysis Set that were enrolled in the Safety Run-In. The Safety Analysis Set includes all participants who received any amount of study drug.

Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only)

The Full Analysis Set includes all participants who received any amount of study drug.

Confirmed Objective Response Rate (ORR) (Part B)

Any TEAE

Treatment-related TEAE

Treatment-related Grade 3-4 TEAE

Treatment-related Grade 5 TEAE

Max severity of TEAE - Grade 1

Max severity of TEAE - Grade 2

Max severity of TEAE - Grade 3

Max severity of TEAE - Grade 4

Max severity of TEAE - Grade 5

Any treatment-emergent serious AE (SAE)

Treatment-related SAE

Number of Participants With Adverse Events (AEs) (Part B)

Confirmed and Unconfirmed ORR (Part B)

The CA-125 evaluable analysis set includes participants who have an elevated baseline CA-125 value of ≥2 x ULN (upper limit of normal) within 2 weeks prior to the first dose of study drug.

Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B)

Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B)

Subset of the Full Analysis Set includes all participants who received any amount of study drug and had a confirmed CR or PR.

Duration of Response (DOR) (Part B)

The Full Analysis Set includes all participants who received any amount of study drug

Disease Control Rate (DCR) (Part B)

Time to Response (TTR) (Part B)

Progression-free Survival (PFS) (Part B)

Overall Survival (OS) (Part B)

Baseline Negative - Negative post-baseline

Baseline Negative - Positive post-baseline

Baseline Positive - Negative post-baseline

Baseline Positive - Positive post-baseline

Participants in the Safety Analysis Set with a baseline and at least one post-baseline ATA sample.

Incidence of Antitherapeutic Antibodies (ATA) (Part B)

Cycle 1, Dose 1

Cycle 1, Dose 3

PK analysis set which includes enrolled participants who received any amount of study drug and at least one PK parameter can be estimated.

Pharmacokinetic (PK) Parameter: Antibody-Drug Conjugate (ADC) Maximum Concentration (Cmax) (Part B)

PK Parameter: ADC Time of Cmax (Tmax) (Part B)

Cycle 1, Dose 1 - AUC 7 Days-ADC

Cycle 1, Dose 3 - AUC 7 Days-ADC

Cycle 1, Dose 3 - AUC 14 Days-ADC

PK Analysis Set includes enrolled participants who received any amount of study drug and at least one PK parameter can be estimated.

PK Parameter: ADC Area Under Concentration-Time Curve (AUC) (Part B)

PK Parameter: Free Monomethyl Auristatin E (MMAE) Cmax (Part B)

PK Parameter: MMAE Tmax (Part B)

Cycle 1, Dose 1 - AUC Last-MMAE

Cycle 1, Dose 3 - AUC Last-MMAE

PK Parameter: MMAE AUC (Part B)

PK Parameter: MMAE Trough Concentration (Ctrough) (Part B)

PK Parameter: Total Antibody (TAb) Cmax (Part B)

PK Parameter: TAb Tmax (Part B)

Cycle 1, Dose 1 - AUC 7 Days-TAb

Cycle 1, Dose 3 - AUC 7 Days-TAb

Cycle 1, Dose 3 - AUC 14 Days-TAb

PK Parameter: TAb Area Under Concentration-Time Curve (AUC) (Part B)

Tisotumab Vedotin 2.0 mg/kg by IV infusion on Day 1 of each 3-week treatment cycle

Part A Q3W

Tisotumab Vedotin by IV infusion on Days 1, 8, and 15 of every 4-week cycle

Part A 3Q4W

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pharmaceutical Solutions

A complete treatment cycle is defined as 21 calendar days. TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle

TUB-040

Ines Vasconcelos Medical Director, MD

Dagmar Siebold, PhD

Alexander Starodub

Alexander Starodub, MD

Shiraj Sen, MD

Alexander Spira, MD

Guenter Fingerle-Rowson, MD, PhD

The purpose of this multicentric, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in patients with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of two parts: In dose escalation, ovarian cancer patients and lung cancer patients receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for patients.

TUB-040 is given IV every 3 weeks until the disease progresses or the patient has to stop due to side effects.

FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC

A First-in-human Dose Escalation and Optimization Phase I/IIa Study to Investigate Safety, Tolerability, PK, and Efficacy of the NaPi2b ADC TUB-040 in Patients With Platinum-resistant High-grade Ovarian Cancer (PROC) or r/r Adenocarcinoma Non-small Cell Lung Cancer (NSCLC)

we first want to evaluate the ICMJE Guidelines

The highest dose is defined at which no more than 1 of 3 patients have had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmax will be derived).

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived).

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Tmax will be derived).

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (AUC will be derived).

The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (T1/2 will be derived).

Number and percentage of patients developing anti-TUB-040 antibodies, and semiquantitative titer assessment. It is measured at cycles 1, 2, 3, 4, 6, 8, 10, post treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)	NCT03657043	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	tisotumab vedot...	18 Years -	Seagen Inc.
A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)	NCT03657043	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	tisotumab vedot...	18 Years -	Seagen Inc.
FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC	NCT06303505	Ovarian Cancer Non-small Cell ...	TUB-040	18 Years -	Tubulis GmbH
FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC	NCT06303505	Ovarian Cancer Non-small Cell ...	TUB-040	18 Years -	Tubulis GmbH

Spots Global Cancer Trial Database for proc

Every month we try and update this database with for proc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for proc

Every month we try and update this database with for proc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for proc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.