Clinical trial NCT02001623: Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors
Official title: First-in-human, Dose-escalating Safety Study of Tissue Factor Specific Antibody Drug Conjugate Tisotumab Vedotin (HuMax® TF ADC) in Patients With Locally Advanced and/or Metastatic Solid Tumors Known to Express Tissue Factor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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)
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genmab
First posted: 2013-12-05
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Escalation phase for dose finding followed by expansion phase
Primary purpose: TREATMENT

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.

Detailed description: The study is conducted in two parts. The dose escalation portion of the trial subjects are enrolled into cohorts at increasing dose levels of HuMax-TF-ADC in 21 day treatment cycles.

In the Cohort Expansion part of the trial, will further explore the recommended phase 2 dose of HuMax-TF-ADC as determined in Part 1

Eligibility criteria: Inclusion Criteria:

- 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.

Exclusion Criteria:

* 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.
* Known past or current malignancy other than inclusion diagnosis, except for:
* Cervical carcinoma of Stage 1B or less.
* Non-invasive basal cell or squamous cell skin carcinoma.
* Non-invasive, superficial bladder cancer.
* Prostate cancer with a current PSA level \< 0.1 ng/mL.
* Any curable cancer with a complete response (CR) of \> 5 years duration.
* Known human immunodeficiency virus seropositivity.
* Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B
* Positive serology for hepatitis C based on test at screening.
* Inflammatory bowel disease including Crohn's disease and colitis ulcerosa.
* Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.
* Ongoing acute or chronic inflammatory skin disease.

Primary outcomes:
measure: Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events
timeFrame: 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.
measure: Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events
timeFrame: 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:
measure: Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation Part: AUC0-inf of Free MMAE
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Cmax of Free MMAE
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Tmax of Free MMAE
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE
timeFrame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
measure: Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Objective Response Rate
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Escalation and Expansion Part: Disease Control Rate
timeFrame: At 6, 12, 24 and 36 weeks
measure: Dose Escalation and Expansion Part: Progression Free Survival (PFS)
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
measure: Dose Expansion Part: Duration of Response (DOR)
timeFrame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center (UCIMC)
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: University Gynecologic Oncology
state: Georgia
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Flemish Brabant
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
state: Hainaut
city: Mons
country: Belgium
facility: Centre Hospitalier Universitaire Ambroise Paré
state: Hainaut
city: Yvoir
country: Belgium
facility: CHU UCL Namur - site Godinne
state: Namur
city: Brussels
country: Belgium
facility: Saint-Luc University Hospital
city: Liège
country: Belgium
facility: CHU de Liège
city: Namur
country: Belgium
facility: CHU UCL Namur - Sainte Elisabeth
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Copenhagen University Hospital
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
state: Solna
city: Linköping
country: Sweden
facility: Lungemedicinska Kliniken
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals
state: England
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute - London
state: England
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust
state: Newcastle
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust
state: Wales
city: Glasgow
country: United Kingdom
facility: Beatson Cancer Centre
city: London
country: United Kingdom
facility: Guys hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust
name: Johann de Bono, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.