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

Primary Purpose

Ovary Cancer, Cervix Cancer, Endometrium Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Tisotumab vedotin (HuMax-TF-ADC)

About this trial

This is an interventional treatment trial for Ovary Cancer focused on measuring ovary cancer, cervix cancer, endometrium cancer, bladder cancer, prostate cancer (CRPC), esophagus cancer, lung cancer (NSCLC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.

Exclusion Criteria:

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).
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.
Prior therapy with a conjugated or unconjugated auristatin derivative.
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.
Breast cancer in BRCA1 or BRACA2 positive ovarian cancer patients.
Any curable cancer with a complete response (CR) of > 5 years duration.
Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor.
Ongoing, significant , uncontrolled medical condition.
Presence of peripheral neuropathy.
Active viral, bacterial or fungal infection requiring intravenous treatment with antimicrobial therapy starting less than four weeks prior to first dose.
Oral treatment with antimicrobial therapy starting less than two weeks prior to first dose.
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.
Active ocular surface disease at baseline (based on ophthalmological evaluation).
History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tisotumab vedotin (HuMax-TF-ADC)

Arm Description

Outcomes

Primary Outcome Measures

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.

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

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.

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

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.

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

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.

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.

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.

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.

Secondary Outcome Measures

Part 1: Number of Participants With Markedly Abnormal Laboratory Values

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade >=3 laboratory abnormality events.

Part 2: Number of Participants With Markedly Abnormal Laboratory Values

Part 1: Number of Participants Who Experienced a Skin Rash

Part 2: Number of Participants Who Experienced a Skin Rash

Part 1: Number of Participants Who Experienced a Bleeding Event

Part 2: Number of Participants Who Experienced a Bleeding Event

Part 1: Number of Participants Who Experienced a Neuropathy Event

Part 2: Number of Participants Who Experienced a Neuropathy Event

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).

Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC)

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.

Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC)

Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC)

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.

Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC)

Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined.

Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC)

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined.

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated)

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.

Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated)

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.

Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated)

CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.

Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated)

Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated)

Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)

Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)

Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE)

Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result

Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result

Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage

Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements

Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study

Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study

Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study

Part 1: Best Overall Response (OR)

Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Part 2: Best Overall Response (OR)

Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Part 1: Number of Participants Who Experienced Disease Control

Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later.

Part 2: Number of Participants Who Experienced Disease Control

Part 1: Progression Free Survival (PFS)

Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.

Part 2: Progression Free Survival (PFS)

Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.

Part 1: Duration of Response

Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the date of first progressive disease (PD) or death.

Part 2: Duration of Response

Full Information

NCT ID

NCT02552121

First Posted

September 14, 2015

Last Updated

March 15, 2021

Sponsor

Seagen Inc.

Collaborators

Genmab

1. Study Identification

Unique Protocol Identification Number

NCT02552121

Brief Title

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

Official Title

Dose-escalating and Cohort Expansion Safety Trial 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

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

November 30, 2015 (Actual)

Primary Completion Date

December 13, 2017 (Actual)

Study Completion Date

December 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Seagen Inc.

Collaborators

Genmab

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The study is conducted in two parts. In the Dose Escalation portion of the trial, subjects are enrolled into cohorts at increasing dose levels of tisotumab vedotin (HuMax-TF-ADC) in 28 day treatment cycles. The Cohort Expansion portion of the trial will further explore the recommended phase 2 dose of tisotumab vedotin (HuMax-TF-ADC) as determined in Part 1.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tisotumab vedotin (HuMax-TF-ADC)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Tisotumab vedotin (HuMax-TF-ADC)

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

Part 1: Number of Participants With Markedly Abnormal Laboratory Values

Description

Time Frame

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

Title

Part 2: Number of Participants With Markedly Abnormal Laboratory Values

Description

Time Frame

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

Title

Part 1: Number of Participants Who Experienced a Skin Rash

Time Frame

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

Title

Part 2: Number of Participants Who Experienced a Skin Rash

Time Frame

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

Title

Part 1: Number of Participants Who Experienced a Bleeding Event

Time Frame

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

Title

Part 2: Number of Participants Who Experienced a Bleeding Event

Time Frame

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

Title

Part 1: Number of Participants Who Experienced a Neuropathy Event

Time Frame

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

Title

Part 2: Number of Participants Who Experienced a Neuropathy Event

Time Frame

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

Title

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Time Frame

Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1

Title

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.

Time Frame

Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1

Title

Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Time Frame

Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1

Title

Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Time Frame

Title

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Time Frame

Before infusion of Day 1, 8 and 15 of Cycle 1

Title

Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.

Time Frame

Title

Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC)

Description

Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined.

Time Frame

Title

Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined.

Time Frame

Title

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Time Frame

Title

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.

Time Frame

Title

Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Time Frame

Title

Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Time Frame

Title

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.

Time Frame

Title

Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated)

Description

CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.

Time Frame

0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1

Title

Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.

Time Frame

Title

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated)

Description

Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Time Frame

Before infusion on Day 1, 8 and 15 of Cycle 1

Title

Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)

Time Frame

Title

Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)

Time Frame

Title

Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)

Time Frame

Title

Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)

Description

Time Frame

Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1

Title

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE)

Description

Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.

Time Frame

Before infusion on Day 1, 8 and 15 of Cycle 1

Title

Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result

Time Frame

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

Title

Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result

Time Frame

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

Title

Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage

Time Frame

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

Title

Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements

Time Frame

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

Title

Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study

Time Frame

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

Title

Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study

Time Frame

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

Title

Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study

Time Frame

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

Title

Part 1: Best Overall Response (OR)

Description

Time Frame

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

Title

Part 2: Best Overall Response (OR)

Description

Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Time Frame

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

Title

Part 1: Number of Participants Who Experienced Disease Control

Description

Time Frame

6, 12, 24 and 36 weeks post first infusion (Part 1)

Title

Part 2: Number of Participants Who Experienced Disease Control

Description

Time Frame

6, 12, 24 and 36 weeks post first infusion (Part 2)

Title

Part 1: Progression Free Survival (PFS)

Description

Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.

Time Frame

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

Title

Part 2: Progression Free Survival (PFS)

Description

Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.

Time Frame

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

Title

Part 1: Duration of Response

Description

Time Frame

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

Title

Part 2: Duration of Response

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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. Exclusion Criteria: 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). 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. Prior therapy with a conjugated or unconjugated auristatin derivative. 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. Breast cancer in BRCA1 or BRACA2 positive ovarian cancer patients. Any curable cancer with a complete response (CR) of > 5 years duration. Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor. Ongoing, significant , uncontrolled medical condition. Presence of peripheral neuropathy. Active viral, bacterial or fungal infection requiring intravenous treatment with antimicrobial therapy starting less than four weeks prior to first dose. Oral treatment with antimicrobial therapy starting less than two weeks prior to first dose. 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. Active ocular surface disease at baseline (based on ophthalmological evaluation). History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Johann de Bono, Professor

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Institut Jules Bordet

City

Bruxelles

State/Province

Brussels

ZIP/Postal Code

1000

Country

Belgium

Facility Name

Universitaire Ziekenhuizen Leuven

City

Leuven

State/Province

Flemish Brabant

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Grand Hôpital de Charleroi

City

Charleroi

State/Province

Hainaut

ZIP/Postal Code

6000

Country

Belgium

Facility Name

CHU de Liège

City

Liege

State/Province

Liège

ZIP/Postal Code

4000

Country

Belgium

Facility Name

CHU UCL Namur - site Godinne

City

Yvoir

State/Province

Namur

ZIP/Postal Code

5530

Country

Belgium

Facility Name

Cliniques Universitaires Saint-Luc

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

CHU UCL Namur - Sainte Elisabeth

City

Namur

ZIP/Postal Code

5000

Country

Belgium

Facility Name

Rigshospitalet, Copenhagen University Hospital

City

Copenhagen

ZIP/Postal Code

DK-2100

Country

Denmark

Facility Name

Petz Aladár Megyei Oktató Kórház

City

Gyor

State/Province

Gyor-Moson-Sopron

ZIP/Postal Code

9023

Country

Hungary

Facility Name

Debreceni Egyetem Klinikai Központ

City

Debrecen

State/Province

Hajdu-Bihar

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Semmelweis Egyetem Onkológiai Központ

City

Budapest

ZIP/Postal Code

1083

Country

Hungary

Facility Name

University College London Hospitals NHS Foundation Trust

City

London

State/Province

England

ZIP/Postal Code

NW1 2PG

Country

United Kingdom

Facility Name

Sarah Cannon Cancer Center

City

London

State/Province

England

ZIP/Postal Code

W1G 6AD

Country

United Kingdom

Facility Name

The Christie NHS Foundation Trust

City

Manchester

State/Province

England

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

The Royal Marsden NHS Foundation Trust

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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

Ovary Cancer, Cervix Cancer, Endometrium Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial