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

NCT02001623 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GEN701innovaTV 201
• Study Type: interventional
• Target: 195
• Locations: 5 countries
• Sites: 29

Brief Summary

The purpose of the trial is to establish the tolerability of HuMax-TF-ADC 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); Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Keywords

ovary cancer; cervix cancer; endometrium cancer; bladder cancer; prostate cancer (CRPC); esophagus cancer; lung cancer(NSCLC); Squamous cell carcinoma of the head and neck (SCCHN)

Outcome Measures

Primary Outcomes (2)

• Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events

  Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

  Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the dose escalation part.

• Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events

  Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

  Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 325 days in the dose expansion part.

Secondary Outcomes (27)

• Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values

  Day 1 to end of follow-up, up to a maximum of 60 weeks

• Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values

  Day 1 to end of follow-up, up to a maximum of 60 weeks

• Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values

  Day 1 to end of follow-up, up to a maximum of 60 weeks

• Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash

  Day 1 to end of follow-up, up to a maximum of 60 weeks

• Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest

  Day 1 to end of follow-up, up to a maximum of 60 weeks

Study Arms (1)

Tisotumab Vedotin (HuMax-TF-ADC)

EXPERIMENTAL

All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC)

Drug: Tisotumab Vedotin (HuMax-TF-ADC)

Interventions

Tisotumab Vedotin (HuMax-TF-ADC) DRUG

Also known as: TIVDAK

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
• Age ≥ 18 years.
• Acceptable renal function
• Acceptable liver function
• Acceptable hematological status (without hematologic support
• 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.
• Ongoing major 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.
• 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 ≥ 100 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.
• Major surgery within six weeks or open biopsy within 14 days before drug infusion.
• Plan for any major surgery during treatment period.
• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.
• Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within four weeks or five half lives, whichever is longest, before first infusion.
• Prior treatment with bevacizumab within twelve weeks before the first infusion.
• Radiotherapy within 28 days prior to first dose.
• Patients who have not recovered from symptomatic side effects of radiotherapy at the time of initiation of screening procedure.
• Cervical carcinoma of Stage 1B or less.
• Non-invasive basal cell or squamous cell skin carcinoma.

Sponsors & Collaborators

• Seagen Inc.: lead
• Genmab: collaborator

Study Sites (29)

University of California Irvine Medical Center (UCIMC)

Orange, California, 92868-3201, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University Gynecologic Oncology

Atlanta, Georgia, 30342, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Universitair Ziekenhuis Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, Flemish Brabant, 3000, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, Hainaut, 6000, Belgium

Location

Centre Hospitalier Universitaire Ambroise Paré

Mons, Hainaut, 7000, Belgium

Location

CHU UCL Namur - site Godinne

Yvoir, Namur, 5530, Belgium

Location

Saint-Luc University Hospital

Brussels, 1200, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

CHU UCL Namur - Sainte Elisabeth

Namur, 5000, Belgium

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, DK-2100, Denmark

Location

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

Karolinska Universitetssjukhuset

Stockholm, Solna, 17176, Sweden

Location

Lungemedicinska Kliniken

Linköping, 58185, Sweden

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, England, LS9 7TF, United Kingdom

Location

University College London Hospitals

London, England, NW1 2BU, United Kingdom

Location

Sarah Cannon Research Institute - London

London, England, W1G 6AD, United Kingdom

Location

Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, Newcastle, NE7 7DN, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Velindre NHS Trust

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Beatson Cancer Centre

Glasgow, G12 OYN, United Kingdom

Location

Guys hospital

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (4)

• de Bono JS, Concin N, Hong DS, Thistlethwaite FC, Machiels JP, Arkenau HT, Plummer R, Jones RH, Nielsen D, Windfeld K, Ghatta S, Slomovitz BM, Spicer JF, Yachnin J, Ang JE, Mau-Sorensen PM, Forster MD, Collins D, Dean E, Rangwala RA, Lassen U. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Mar;20(3):383-393. doi: 10.1016/S1470-2045(18)30859-3. Epub 2019 Feb 8.

  PMID: 30745090 RESULT

• 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

• Hong DS, Concin N, Vergote I, de Bono JS, Slomovitz BM, Drew Y, Arkenau HT, Machiels JP, Spicer JF, Jones R, Forster MD, Cornez N, Gennigens C, Johnson ML, Thistlethwaite FC, Rangwala RA, Ghatta S, Windfeld K, Harris JR, Lassen UN, Coleman RL. Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer. Clin Cancer Res. 2020 Mar 15;26(6):1220-1228. doi: 10.1158/1078-0432.CCR-19-2962. Epub 2019 Dec 3.

  PMID: 31796521 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Urinary Bladder Neoplasms; Prostatic Neoplasms; Esophageal Neoplasms; Squamous Cell Carcinoma of Head and Neck

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; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Genmab A/S

clinicaltrials@genmab.com

70202728

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

Model Details: Escalation phase for dose finding followed by expansion phase

Study Record Dates

• First Submitted: November 14, 2013
• First Posted: December 5, 2013
• Study Start: November 30, 2013
• Primary Completion: May 2, 2019
• Study Completion: May 2, 2019
• Last Updated: December 29, 2021
• Results First Posted: December 29, 2021

Record last verified: 2021-11

Locations

SE (2); US (8); DK (2); GB (9); BE (8)