Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors

NCT02552121 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GEN702innovaTV 202
• Study Type: interventional
• Target: 33
• Locations: 5 countries
• Sites: 16

Brief Summary

The purpose of the trial is to establish the tolerability of tisotumab vedotin (HuMax-TF-ADC) dosed three times every four weeks (3q4wk) in a mixed population of patients with specified solid tumors.

Conditions

Ovary Cancer; Cervix Cancer; Endometrium Cancer; Bladder Cancer; Prostate Cancer (CRPC); Esophagus Cancer; Lung Cancer (NSCLC)

Keywords

ovary cancer; cervix cancer; endometrium cancer; bladder cancer; prostate cancer (CRPC); esophagus cancer; lung cancer (NSCLC)

Outcome Measures

Primary Outcomes (10)

• Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Baseline to end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE)

  A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE)

  A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.

  Baseline to end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events

  An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.

  Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks

• Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events

  An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.

  Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events

  A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events

  A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.

  Baseline to end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events

  A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events

  A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.

  Baseline to end of trial (Part 2), up to 36 weeks

Secondary Outcomes (52)

• Part 1: Number of Participants With Markedly Abnormal Laboratory Values

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants With Markedly Abnormal Laboratory Values

  Baseline to end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Who Experienced a Skin Rash

  Baseline to end of follow-up; maximum time of follow-up was 24 weeks

• Part 2: Number of Participants Who Experienced a Skin Rash

  Baseline to end of trial (Part 2), up to 36 weeks

• Part 1: Number of Participants Who Experienced a Bleeding Event

  Baseline to end of trial (Part 1), up to 72 weeks

Study Arms (1)

Tisotumab vedotin (HuMax-TF-ADC)

EXPERIMENTAL

Drug: Tisotumab vedotin (HuMax-TF-ADC)

Interventions

Tisotumab vedotin (HuMax-TF-ADC) DRUG

Tisotumab vedotin (HuMax-TF-ADC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy.
• Patients must have measurable disease according to RECIST v1.1
• Age ≥ 18 years.
• Acceptable renal function.
• Acceptable liver function.
• Acceptable hematological status (hematologic support allowed under certain circumstances).
• Acceptable coagulation status.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least three months.
• A negative serum pregnancy test (if female and aged between 18-55 years old).
• Women who are pregnant or breast feeding are not to be included.
• Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of HuMax-TF-ADC.
• Following receipt of verbal and written information about the study, patients must provide signed informed consent before any study-related activity is carried out.

You may not qualify if:

• Known past or current coagulation defects.
• Diffuse alveolar hemorrhage from vasculitis.
• Known bleeding diathesis.
• Ongoing major bleeding.
• Trauma with increased risk of life-threatening bleeding.
• Have clinically significant cardiac disease.
• A baseline QT interval as corrected by Fridericia's formula (QTcF) \> 450 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block.
• Therapeutic anti-coagulative or long term anti-platelet treatment except use of low dose acetylsalicylic acid (ASA) up to 81 mg/day and non-ASA nonsteroidal anti-inflammatory drugs (NSAIDs).
• Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within one week or pegylated G-CSF within two weeks before the Screening Visit.
• Have received a cumulative dose of corticosteroid ≥ 150 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.
• No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium.
• Major surgery within six weeks or open biopsy within 14 days before drug infusion.
• Plan for any major surgery during treatment period.
• Patients not willing or able to have a pre-trial tumor biopsy taken (the screening biopsy can be omitted if archived material is available).
• Presence or anticipated requirement of epidural catheter in relation to infusions (within 48 hours before and after dose of trial drug).

Sponsors & Collaborators

• Seagen Inc.: lead
• Genmab: collaborator

Study Sites (16)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Jules Bordet

Brussels, Brussels Capital, 1000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Flemish Brabant, 3000, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, Hainaut, 6000, Belgium

Location

CHU de Liège

Liège, Liège, 4000, Belgium

Location

CHU UCL Namur - site Godinne

Yvoir, Namur, 5530, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

CHU UCL Namur - Sainte Elisabeth

Namur, 5000, Belgium

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, DK-2100, Denmark

Location

Petz Aladár Megyei Oktató Kórház

Győr, Győr-Moson-Sopron, 9023, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Semmelweis Egyetem Onkológiai Központ

Budapest, 1083, Hungary

Location

University College London Hospitals NHS Foundation Trust

London, England, NW1 2PG, United Kingdom

Location

Sarah Cannon Cancer Center

London, England, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Feng S, Gunawan R, Passey C, Voellinger J, Polhamus D, Gerritsen A, O'Day C, Carret AS, Soumaoro I, Gupta M, Hanley WD. Exposure-safety Markov modeling of ocular adverse events in patient populations treated with tisotumab vedotin. J Pharmacokinet Pharmacodyn. 2025 Oct 3;52(5):55. doi: 10.1007/s10928-025-10003-w.

  PMID: 41044356 DERIVED

• Passey C, Voellinger J, Gibiansky L, Gunawan R, Nicacio L, Soumaoro I, Hanley WD, Winter H, Gupta M. Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. CPT Pharmacometrics Syst Pharmacol. 2023 Sep;12(9):1262-1273. doi: 10.1002/psp4.13007. Epub 2023 Jul 26.

  PMID: 37496366 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Urinary Bladder Neoplasms; Prostatic Neoplasms; Esophageal Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

tisotumab vedotin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Genmab
• Organization: Genmab A/S

clinicaltrials@genmab.com

7020 2728

Study Officials

• Johann de Bono, Professor

  The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2015
• First Posted: September 16, 2015
• Study Start: November 30, 2015
• Primary Completion: December 13, 2017
• Study Completion: December 13, 2017
• Last Updated: April 8, 2021
• Results First Posted: March 12, 2019

Record last verified: 2021-03

Locations

DK (1); US (1); BE (7); GB (4); HU (3)