sacituzumab govitecan for Metastatic solid tumors

Inclusion criteria

• {"criterion_text":"- Subjects meeting all the following inclusion criteria at Screening will be eligible for participation in the study. Female or male subjects, > 18 years of age, who are able to understand and give written informed consent.\n- Tumor blocks (preferably obtained within 12 months of study entry if clinically feasible) or 20 newly sectioned unstained slides (6 slides minimum) of archived biopsy/surgical specimens are requested. A baseline biopsy is required if archival tissue is not available. Fine needle aspirates and bone biopsies are not suitable samples. These specimens should be submitted within the 28-day screening period, after the subject provides written informed consent.\n- Subjects with the following histologically documented metastatic (M1, Stage IV) or locally advanced solid tumors. 2.1\tNSCLC (adenocarcinoma or SCC) that has progressed after prior platinum-based chemotherapy and programmed death-(ligand) 1 (PD- (L)1) directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. If subjects have had recurrence/relapse or lack of response within 6 months of completing chemotherapy with or without PD-(L)1 directed therapy for locally advanced disease, that line of therapy may be counted for eligibility. 2.2\tHNSCC that has progressed after prior platinum-based chemotherapy and anti-PD-(L)1 directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. No more than 3 prior lines of systemic treatment is allowed. 2.3\tEndometrial carcinoma that has progressed after prior platinum-based chemotherapy and anti- PD-(L)1 directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. No more than 3 prior lines of systemic treatment is allowed. Endometrial carcinoma with any histology including microsatellite instability-high /mismatch repair deficient and microsatellite stable (MSI-h/dMMR and MSS) are allowed. 2.4\tExtensive stage SCLC that has progressed after prior platinum-based chemotherapy and PD-(L)1 directed therapy. No more than one prior line of systemic treatment is allowed (re-challenge with the same initial regimen is not allowed).\n- ECOG Performance Status score of 0 or 1.\n- Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500/mm3, and platelets ≥ 100,000/μL).\n- Adequate hepatic function (bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] ≤ 2.5 × IULN or ≤ 5 × IULN if known liver metastases and serum albumin > 3 g/dL).\n- Creatinine clearance ≥ 30 mL/min as assessed by Cockcroft-Gault.\n- Subjects must have at least a 3-month life expectancy.\n- Have measurable disease by CT or MRI scan as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area may be utilized if they are considered measurable and PD has been demonstrated in such lesions\n- Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception."}

Exclusion criteria

• {"criterion_text":"- Subjects meeting any of the following exclusion criteria at Screening will not be enrolled in the study. Positive serum pregnancy test (Appendix 17.5) or women who are lactating.\n- Have an active infection requiring IV antibiotics.\n- Have positive human immunodeficiency virus (HIV)-1 or HIV-2 antibody with detectable viral load or taking medications that may interfere with SN-38 (the active metabolite of sacituzumab govitecan).\n- Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), subjects with a detectable viral load will be excluded. 12.1\tSubjects who test positive for hepatitis B surface antigen (HBsAg). Subjects who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. 12.2\tSubjects who test positive for HCV antibody. Subjects who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Subjects with a known history of HCV or a positive HCV antibody test will not require an HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.\n- Have other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.\n- Impending need for palliative radiation therapy or surgery for pathological fractures and/or for medullary compression within 4 weeks prior to initiating study treatment\n- Additional cohort-specific exclusion criteria:- NSCLC cohort (adenocarcinoma and SCC): 15.1\tClinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy. - HNSCC cohort: 15.2\tSubjects with nasopharynx carcinoma. 15.3\tSubjects who had progressive disease within 6 months of completion of curative therapy. - Endometrial carcinoma cohort: 15.4\tSubjects who have carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and/or endometrial stromal sarcomas. - Small cell lung cancer cohort: 15.5\tSubjects who never received platinum-containing regimen for SCLC. 15.6\tLimited-stage subjects who are candidates for local or regional therapy.\n- Are currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of study drug. Subjects participating in observational studies are eligible.\n- Have had a prior anti-cancer biologic agent within 4 weeks prior to study Day 1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.\n- Have not recovered (ie, ≤ Grade 1) from AEs due to a previously administered agent.\n- Have previously received topoisomerase I inhibitors (for SCLC cohort: Etoposide with platinum combination in first-line setting is allowed).\n- Have an active second malignancy.\n- Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, no evidence of new or enlarging brain metastases and are taking ≤ 20 mg/day of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.\n- Have active cardiac disease, defined as: 8.1\tMyocardial infarction or unstable angina pectoris within 6 months of Day 1. 8.2\tHistory of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication); history of QT interval prolongation. 8.3\tNew York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%.\n- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease), immune-mediated colitis, or gastrointestinal (GI) perforation within 6 months of C1D1."}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR) according to RECIST 1.1 by Investigator's assessment.","definition_or_measurement_approach":"According to RECIST 1.1 by Investigator's assessment."}

Secondary endpoints

• {"endpoint_text":"- ORR, DOR, CBR, and PFS according to RECIST 1.1 by BICR.","definition_or_measurement_approach":"Measured according to RECIST 1.1 by Blinded Independent Central Review (BICR)."}
• {"endpoint_text":"- DOR, CBR, and PFS, according to RECIST 1.1 by Investigator's assessment.","definition_or_measurement_approach":"Measured according to RECIST 1.1 by Investigator's assessment."}
• {"endpoint_text":"- Overall survival (OS).","definition_or_measurement_approach":"Overall survival as time from baseline to death from any cause."}
• {"endpoint_text":"- Incidence of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities.","definition_or_measurement_approach":"Standard safety reporting of treatment-emergent AEs and clinical laboratory assessments over time."}
• {"endpoint_text":"- Serum concentrations of sacituzumab govitecan over time and incidence of anti-drug antibody (ADA) to sacituzumab govitecan.","definition_or_measurement_approach":"Pharmacokinetic measurement of serum concentrations over time and immunogenicity testing for anti-drug antibodies."}

Belgium

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

119

Number Of Sites

2

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

112

Number Of Sites

4

Number Of Participants

9

France

Earliest CTIS Part Ii Submission Date

03-07-2024

Latest Decision Or Authorization Date

24-09-2024

Processing Time Days

83

Number Of Sites

4

Number Of Participants

12

Primary sponsor

Full Name

Gilead Sciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Monitoring, Regulatorypreparation of applications to CA and ethics committee), Investigator recruitment, IVRS30 – treatment randomization,

Name

Bioclinica Inc.

Responsibilities

Medical image analysis/ review - X-ray, MRI, ultrasound, etc.

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Monitoring, Regulatorypreparation of applications to CA and ethics committee), Investigator recruitment, IVRS30 – treatment randomization,","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Laboratory/Research/Testing facility"}