Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors
- Conditions
- ocally Advanced or Metastatic Disease in Solid TumorsMedDRA version: 20.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10033599Term: Pancreatic adenocarcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10033600Term: Pancreatic adenocarcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10051971Term: Pancreatic adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10059326Term: Pancreatic carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10033610Term: Pancreatic carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2017-005076-26-FR
- Lead Sponsor
- Seattle Genetics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
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 for locally advanced or metastatic disease. Patients must have received prior therapy with a platinum-based regimen, a tyrosine kinase inhibitor (TKI; ALK, ROS-1 gene rearrangement or EGFR mutation), and a CPI if eligible for such therapy. Patients should have received no more than 2 systemic regimens in the locally advanced or 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 for recurrent or metastatic disease. Patients must not have tumors involving or adjacent to major blood vessels or a history of radiation involving major blood vessels in the radiation field. Patients must have received prior therapy with a platinum-based regimen and/or a CPI if eligible for such therapy. Patients eligible to receive anti-EGFR therapy must have received anti-EGFR therapy prior to study entry. Patients should have received no more than 2 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.
? 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 at least 2 weeks after growth factor support, if applicable.
? platelet count =100 x 109/L assessed at least 2 wee
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.
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. Lesions adjacent to or involving critical anatomical sites, including major blood vessels, mediastinum, and leptomeningeal disease.
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 trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. 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.
1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: This study will evaluate the antitumor activity, safety, and pharmacokinetics (PK) of tisotumab vedotin in patients with locally advanced or metastatic tumors.;Secondary Objective: - Evaluate the safety and tolerability of tisotumab vedotin<br>- Evaluate preliminary antitumor activity of tisotumab vedotin<br>- Evaluate stability and control of disease<br>- Evaluate durability of response in patients who respond to tisotumab vedotin<br>- Evaluate the timing of responses<br>- Evaluate progression-free survival (PFS) of patients treated with tisotumab vedotin<br>- Evaluate survival of patients treated with tisotumab vedotin<br>- Assess pharmacokinetics of tisotumab vedotin<br>- Assess immunogenicity of tisotumab vedotin;Primary end point(s): Investigator-determined confirmed ORR as measured by RECIST v1.1;Timepoint(s) of evaluation of this end point: According to protocol.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Safety and tolerability of tisotumab vedotin, as measured by type, incidence, severity, seriousness, and relatedness of AEs<br>- Investigator-determined confirmed and unconfirmed ORR as measured by RECIST v 1.1<br>- Investigator-determined disease control rate (DCR) as measured by RECIST v1.1<br>- Investigator- determined duration of response (DOR) as measured by RECIST v1.1<br>- Investigator- determined time to response (TTR) as measured by RECIST v1.1<br>- Investigator- determined PFS as measured by RECIST v1.1<br>- Overall survival (OS)<br>- Selected PK parameters for tisotumab vedotin and MMAE<br>- Incidence of anti-therapeutic antibodies (ATAs) to tisotumab vedotin;Timepoint(s) of evaluation of this end point: According to protocol.