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: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10033599Term: Pancreatic adenocarcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10033600Term: Pancreatic adenocarcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10051971Term: Pancreatic adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10059326Term: Pancreatic carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 25.1Level: PTClassification code 10033610Term: Pancreatic carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2017-005076-26-DE
• Lead Sponsor: Seagen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-10
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 532

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 3 lines of systemic therapy in the metastatic setting. Maintenance therapy should not be counted as a separate line of therapy.
- 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 4 lines systemic therapy 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 received a prior platinum-based regimen and/or CPI, if eligible, and must have experienced disease progression following such therapy. Patients should have received no more than 3 systemic lines of therapy in the recurrent/metastatic setting. Maintenance therapy should not be counted as a separate line of therapy.
2. Measurable 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:
? (ANC) =1500/µL assessed at least 2 weeks after growth factor support, if applicable.
? platelet count =100 x 109/L assessed at least 2 weeks after transfusion with blood products.
? hemoglobin =5.6 mmol/L (9.0 g/dL) assessed at least 2 weeks after transfusion with blood product

Exclusion Criteria

1. Patients with primary neuroendocrine or sarcomatoid histologies. For SCCHN, patients may not have a primary site of nasopharynx (regardless of histology).
2. 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. Clinically significant cardiac disease; medical history of congestive heart failure (Grade III or IV as classified by the New York Heart Association, see Appendix G); medical history of decreased cardiac ejection fraction of <45%.
4. Ophthalmological: Active ocular surface disease at baseline. Ocular evaluation confirmed by an ophthalmologist at screening. Patients with prior episode of cicatricial conjunctivitis or Steven Johnson syndrome (evaluated by the investigator) are ineligible. Please note that cataract is not considered active ocular surface disease for this protocol.
5. Evidence of malignancy within 3 years of the first dose of study drug, or evidence of residual disease. Exceptions are malignancies with negligible risk of metastasis or death (e.g., 5-year overall survival =90%), such as adequately treated metastatic cancers.
6. Tumor lesions invading, encasing, abutting, or involving critical anatomical sites, such as major blood vessels, (such as internal carotid artery, external carotid artery, pulmonary artery, etc) mediastinal blood vessels, and leptomeningeal disease. Mediastinal lymphadenopathy or invasion of mediastinal connective tissue 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.
Patients with chronic obstructive pulmonary disease are allowed if not requiring systemic steroids and long-term oxygen
11. Medications or treatment regimens:
? therapeutic anti-coagulation therapy is permitted IF the patient is no longer being actively titrated for anti-coagulation. For oral anticoagulation therapy, 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 first dose of trial treatment. Examples include in page 57 of Protocol. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
14. Peripheral neuropathy Grade =2.
15. Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parental hydration and/or nutrition.
16. Prior therapy:
? Prior treatment with MMAE-derived

Study & Design

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