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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02552121
• Date of registration: 14/09/2015
• Prospective Registration: Yes
• Primary sponsor: Genmab
• Public title: Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors
• Scientific 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
• Date of first enrolment: November 30, 2015
• Target sample size: 33
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02552121
• Study type: Interventional
• Study design: Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, Denmark, Hungary, United Kingdom, United States

Contacts

• Name: Johann de Bono, Professor
• Affiliation: The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Prostate Cancer (CRPC)

Lung Cancer (NSCLC)

Cervix Cancer

Endometrium Cancer

Ovary Cancer

Bladder Cancer

Esophagus Cancer

Intervention(s)

Drug: Tisotumab vedotin (HuMax-TF-ADC)

Primary Outcome(s)

Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events [Time Frame: 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 Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events [Time Frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks]

Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events [Time Frame: 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 [Time Frame: 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) [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) [Time Frame: 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 [Time Frame: 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) [Time Frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks]

Secondary Outcome(s)

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

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: 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]

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

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

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) [Time Frame: Before infusion on Day 1, 8 and 15 of Cycle 1]

Part 1: Number of Participants With Markedly Abnormal Laboratory Values [Time Frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks]

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

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) [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]

Part 2: Number of Participants Who Experienced Disease Control [Time Frame: 6, 12, 24 and 36 weeks post first infusion (Part 2)]

Part 2: 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 day 1, and before infusion on days 8 and 15 of Cycle 1]

Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity 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]

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]

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

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

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) [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]

Part 1: Number of Participants Who Experienced a Bleeding Event [Time Frame: Baseline to end of trial (Part 1), up to 72 weeks]

Part 2: Duration of Response [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

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

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]

Part 1: Number of Participants Who Experienced Disease Control [Time Frame: 6, 12, 24 and 36 weeks post first infusion (Part 1)]

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]

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) [Time Frame: Before infusion on Day 1, 8 and 15 of Cycle 1]

Part 1: Total Clearance (CL) of 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]

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]

Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) [Time Frame: Before infusion of Day 1, 8 and 15 of Cycle 1]

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

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]

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

Part 2: Number of Participants Who Experienced a Neuropathy Event [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 2: Number of Participants With Markedly Abnormal Laboratory Values [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

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

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

Part 1: Best Overall Response (OR) [Time Frame: Baseline to end of trial (Part 1), up to 72 weeks]

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]

Part 1: Progression Free Survival (PFS) [Time Frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks]

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

Part 1: Tmax: Time to Reach the Maximum 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]

Part 2: Best Overall Response (OR) [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 2: Number of Participants Who Experienced a Bleeding Event [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Part 2: Number of Participants Who Experienced a Skin Rash [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

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

Part 1: Apparent Volume of Distribution (Vz) 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]

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: 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]

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]

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]

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]

Part 1: Duration of Response [Time Frame: Baseline to end of trial (Part 1), up to 72 weeks]

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]

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]

Part 1: Terminal Phase Elimination Half-life (T1/2) 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]

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) [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]

Part 2: Progression Free Survival (PFS) [Time Frame: Baseline to end of trial (Part 2), up to 36 weeks]

Secondary ID(s)

innovaTV 202

GEN702

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Seagen Inc.

Results

• Results available: Yes
• Date Posted: 12/03/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02552121