Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors

Phase 1

• Conditions: ocally Advanced or Metastatic Disease in Solid Tumors; MedDRA version: 21.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0 Level: LLT Classification code 10033599 Term: Pancreatic adenocarcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0 Level: LLT Classification code 10033600 Term: Pancreatic adenocarcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: LLT Classification code 10051971 Te; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-005076-26-IT
• Lead Sponsor: Seattle Genetics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-21
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 200

Inclusion Criteria

1. Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN that has failed prior lines of systemic treatment as specified and which are not candidates for standard therapy.
? Colorectal Cancer: Patients with colorectal cancer must have experienced disease progression on or after their most recent systemic therapy for non-operable metastatic disease. Isolated increase in carcinoembryonic antigen (CEA) will not qualify for study entry. Patients must have received prior therapy with each of the following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Patients with known/previously-tested RAS wild-type tumors and/or known/previously-tested MSI-H tumors could have received cetuximab or panitumumab and CPI, if eligible. Patients should have received no more than 3 systemic regimens in the metastatic setting.
? NSCLC: Patients with NSCLC must have histologically or cytologically documented squamous cell NSCLC and must have experienced disease progression on or after their most recent systemic therapy. Patients must have received prior therapy for NSCLC with a platinum-based regimen and a CPI, if eligible. Patients should have received no more than 2 systemic regimens in the metastatic setting.
-Patients eligible for a tyrosine kinase inhibitor (TKI; ALK, ROS-1 gene rearrangement, or EGFR mutation) should have received such therapy. These patients should have received no more than 3 systemic regimens in the metastatic setting.
? Exocrine pancreatic adenocarcinoma: Patients with exocrine pancreatic adenocarcinoma must have biopsy proven, histologically confirmed diagnosis of exocrine pancreatic adenocarcinoma and must have experienced disease progression on or after their most recent systemic therapy for locally advanced or metastatic disease. Isolated increase in CA 19-9 or CEA will not qualify for study entry. Patients must have received prior therapy with a gemcitabine-based or 5FU-based regimen if eligible for such therapy. Patients should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
? SCCHN: Patients with SCCHN must have experienced disease progression on or after their most recent systemic therapy. Patients must have received prior therapy with a platinum-based regimen and a CPI, if eligible. Patients eligible to receive anti-epithelial growth factor receptor (anti-EGFR) therapy must have received anti-EGFR therapy prior to study entry. Patients should have received no more than 3 systemic regimens in the recurrent/metastatic setting.
2. Measureable disease according to RECIST v1.1 as assessed by the investigator.
? A minimum of one non-nodal lesion =10 mm in the longest diameter from a non-irradiated area. If target lesion(s) are located within previously irradiated area only, the patient can be enrolled only if there has been demonstrated progression in the in field” lesion and upon approval of the sponsor’s medical monitor. OR
? Lymph node lesion =15 mm in the shortest diameter from a non-irradiated area.
3. Age 18 years or older.
4. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
5. The following baseline laboratory data:
? absolute neutrophil count (ANC) =1500/µL assessed

Exclusion Criteria

1. Patients with primary neuroendocrine or sarcomatoid histologies.
2. Hematological: Known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry.
3. Cardiovascular: Clinically significant cardiac disease including unstable angina, acute myocardial infarction 6 months prior to screening; any medical history of congestive heart failure (Grade III or IV as classified by the New York Heart Association, see Appendix G), any medical history of decreased cardiac ejection fraction of <45%.
4. Ophthalmological: Active ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Patients with any prior episode of cicatricial conjunctivitis or Steven Johnson syndrome (as evaluated by the investigator) are ineligible. Please note that cataract is not considered active ocular surface disease for this protocol.
5. History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival =90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
6. Tumor lesions invading, encasing, abutting, or involving critical anatomical sites, such as major blood vessels, mediastinum, and leptomeningeal disease. Please note that mediastinal lymphadenopathy is not an exclusion
7. Inflammatory bowel disease including Crohn’s disease and colitis ulcerosa.
8. Ongoing, acute or chronic inflammatory skin disease.
9. Uncontrolled tumor-related pain
10. Inflammatory lung disease, including moderate and severe asthma and chronic obstructive pulmonary disease, requiring chronic medical therapy
11. Medications or treatment regimens:
? For patients with SCCHN or NSCLC, therapeutic anti-coagulation is not permitted. For patients with colorectal or pancreatic cancers, therapeutic anti-coagulation therapy is permitted IF the patient is no longer being actively titrated for anti-coagulation. For oral anticoagulation therapy, colorectal and pancreatic patients must be on steady doses for at least 4 weeks prior to the first dose of study drug.
? Chronic prophylactic treatment with ASA (e.g., aspirin) in combination with other anti-coagulation therapy is prohibited.
? Cumulative dose of corticosteroid =150 mg (prednisone or equivalent doses of corticosteroids) within 2 weeks of the first tisotumab vedotin administration is prohibited.
12. Surgery/procedures: Major surgical procedure (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 4 weeks or excisional biopsy within 7 days prior to the first study drug administration. Patients who have planned major surgery during the treatment period must be excluded from the trial.
13. Received a live vaccine within 30 days prior to the first dose of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified