E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cancer of the ovary, cervix, endometrium, bladder, prostate (castration-resistant prostate cancer [CRPC]), esophagus or lung (non-small cell lung cancer [NSCLC]) |
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E.1.1.1 | Medical condition in easily understood language |
Cancers of the ovary, cervix, endometrium, bladder, prostate, esophagus and lung |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10014742 |
E.1.2 | Term | Endometrial neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008342 |
E.1.2 | Term | Cervix carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062878 |
E.1.2 | Term | Gastrooesophageal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023774 |
E.1.2 | Term | Large cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To establish the tolerability of HuMax-TF-ADC dosed three times q4wk in a mixed population of patients with specified solid tumors |
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E.2.2 | Secondary objectives of the trial |
• To determine the MTD and RP2D of HuMax-TF-ADC dosed three times q4wk
• To establish the PK profile of HuMax-TF-ADC dosed three times q4wk
• To evaluate the anti-tumor activity of HuMax-TF-ADC dosed three times q4wk in a mixed population of patients with specified solid tumors
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy.
• Age ≥ 18 years.
• 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.
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E.4 | Principal exclusion criteria |
• Known past or current coagulation defects leading to increased risk of bleeding.
• Ongoing major bleeding
• 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
AEs during the study: Incidences of AEs, SAEs, infusion-related AEs, CTCAE grade ≥ 3 AEs and AEs related to trial drug. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Safety laboratory parameters (hematology, biochemistry, coagulation factors and flow cytometry)
• Skin disorders
• Bleeding events
• Neuropathy
• PK parameters (clearance, volume of distribution and AUC [AUC0-Clast and AUC0-∞], Cmax, time of Cmax [Tmax], pre dose values, and half-life of HuMax-TF-ADC and free toxin [MMAE])
• Immunogenicity of HuMax-TF-ADC (human anti human antibodies)
• Anti-tumor activity measured by tumor shrinkage (based on CT-scan evaluations), change in PSA and CA 125
• Objective Response (Complete Response [CR] or PR), Disease Control (CR, PR or stable disease [SD]), Progression Free Survival (PFS) and Duration of Response (DoR)
Research Endpoints:
• TF expression in tumor biopsies
• Circulating TF
• Circulating cell-free deoxyribonucleic acid (cfDNA)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of trial and as part of preparations for subsequent trials, exploratory analysis of subsets of data may be performed. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Hungary |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |