Cancer of the ovary, cervix, endometrium, bladder, prostate (castration-resistant prostate cancer [CRPC]), head and neck (squamous cell carcinoma of the head and neck [SCCHN]), esophagus or lung (non-small cell lung cancer [NSCLC] MedDRA version: 20.0 Level: HLT Classification code 10014742 Term: Endometrial neoplasms malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Pro
Conditions
Interventions
Product Name: HuMax®-TF-ADC
Product Code: IgG1-1015-011-1006
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: HuMax®-TF-ADC
CAS Number: 1418731-10-1
Current S
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion 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. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 57 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
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. 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. Major surgery within six weeks or open biopsy within 7 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 five half lives before first infusion (for anti-cancer therapies with half-lives > 8 days, a washout period of at least 40 days is acceptable). 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 5 years duration. Known human immunodeficiency virus seropositivity. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the tolerability of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors;Secondary Objective: To establish the long term tolerability of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors. To determine the maximum tolerated dose (MTD) and the recommended dose for phase II trials with HuMax®-TF-ADC . To establish the pharmacokinetic (PK) profile of HuMax®-TF-ADC after single and multiple infusions. To evaluate the anti-tumor activity of HuMax®-TF-ADC in a mixed population of patients with specified solid tumors.;Primary end point(s): AEs during the study: incidences of AEs, SAEs, infusion-related AEs, CTCAE grade = 3 AEs, and AEs related to study drug.;Timepoint(s) of evaluation of this end point: During the entire study | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 area-under-the-concentration-time curve [AUC0 Clast and AUC0-8]), maximum concentration [Cmax], time of Cmax [Tmax], pre-dose values, and half life of HuMax®-TF-ADC and free toxin [MMAE]). - Immunogenicity of HuMax®-TF-ADC (anti-drug antibodies). - Anti-tumor activity measured by tumor shrinkage (based on computerized tomography [CT] scan evaluations), change in PSA and CA 125. - Objective Response (CR or Partial Response [PR]), Disease Control (CR, PR or Stable Disease [SD]), after 6, 12, 24 and 36 weeks, Progression-Free Survival (PFS) and Duration of Response (DoR). Exploratory Endpoints: - TF expression in tumor biopsies - Circulating TF - Protein biomarker - Circulating cell-free deoxyribonucleic acid (cfDNA));Timepoint(s) of evaluation of this end point: At end of trial and as part of preparations for subsequent trials, exploratory analysis of subsets of data may be performed. | — |
Countries
Belgium, Denmark, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Genmab A/S
Outcome results
None listed