SACITUZUMAB GOVITECAN for PD-L1-negative metastatic triple-negative breast cancer | PD-L1-positive metastatic triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"- Patients must meet all of the following inclusion criteria to be eligible for participation in this study (no waivers for patient eligibility will be offered or permitted): Female or male patients, regardless of race and ethnic group, who are 18 years of age or older, able to understand and give written informed consent.\n- International Normalized Ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy.\n- Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 11.3.\n- Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: a) Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening. b) Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening. c) Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1). d) The combination ART regimen must not contain any medications that may interfere with SN-38 metabolism.\n- Patients with locally advanced, inoperable, or metastatic TNBC who have not received previous systemic therapy for advanced disease and whose tumors are PD-L1 negative at screening. Alternatively, patients whose tumors are PD-L1 positive at screening will be eligible if they received an anti-programmed death (ligand) 1 (anti-PD-[L]1) agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting or if they cannot be treated with an anti-PD-(L)1 agent due to a comorbidity. a) Patients must have completed treatment for Stage I-III breast cancer, if indicated, and ≥ 6 months must have elapsed between completion of treatment with curative intent (eg, date of primary breast cancer surgery or date of last (neo)adjuvant chemotherapy administration [including anti-PD-(L)1 treatment], whichever occurred last) and first documented local or distant disease recurrence. Dates of postoperative radiotherapy are not included in this calculation. i) Patients who received taxane, gemcitabine, or platinum agents in the (neo)adjuvant setting can be treated with same class of chemotherapy (taxane or gemcitabine/carboplatin) if ≥ 12 months have elapsed between the completion of treatment with curative intent (eg, date of primary breast tumor surgery or date of last (neo)adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence. ii) Patients enrolled should have received prior anthracycline in the (neo)adjuvant setting or be considered not eligible for anthracyclines as assessed by the treating physician. b) Patients presenting with de novo metastatic TNBC are eligible for this study. c) TNBC status and tumor PD-L1 CPS will be confirmed centrally on a recent or archival tumor specimen. Patients must have histologically or cytologically documented TNBC, according to current ASCO/CAP criteria, defined as negative for ER, progesterone receptor, and HER2 {Allison 2020, Wolff 2018}. Patients initially diagnosed with hormone receptor-positive or HER2-positive breast cancer must have central confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis prior to entry. Tumor combined positive score (CPS) < 10 using the PD-L1 IHC 22C3 assay will be required for eligibility. Alternatively, patients with tumor CPS ≥ 10 will be eligible if they received an anti-PD-(L)1 agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting or if they cannot be treated with an anti-PD-(L)1 agent due to a comorbidity. d) Patients must have measurable disease by CT or MRI as per RECIST Version 1.1 criteria (Appendix 11.6) as evaluated locally. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation.\n- Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in blocks (preferred) or have at least 20 to 25 freshly sectioned unstained slides from fresh biopsy tissue (preferred) or archival tissue block for central testing of ER, progesterone receptor, HER2, and PD-L1 and additional biomarker testing. A baseline biopsy is required if archival tissue is not available and this procedure must be performed prior to the first dose of study treatment and after the patient provides written informed consent. Fine needle B12aspirates and bone biopsies are not suitable samples. Note: Tumor tissue quality must be confirmed by the central laboratory. Submission of another tumor specimen may be required if provided specimen is not adequate for assessment. A discussion with the medical monitor is required if only 15 to 19 unstained slides are available and it is not clinically feasible to obtain a new biopsy.\n- ECOG performance status score of 0 or 1 (see Appendix 11.5).\n- Life expectancy ≥ 3 months.\n- Recovered from major surgery for ≥ 2 weeks.\n- Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).\n- Adequate hepatic function (bilirubin ≤ 1.5  ULN, AST and ALT ≤ 2.5  ULN or ≤ 5 ULN if known liver metastases, and serum albumin > 3 g/dL).\n- Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976}."}

Exclusion criteria

• {"criterion_text":"- Patients who meet any of the following exclusion criteria are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted): Positive serum pregnancy test or women who are lactating (see Appendix 11.3).\n- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment.\n- Have active serious infection requiring antibiotics.\n- Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.\n- Have active HBV (defined as having a positive HBsAg test) or HCV. a) For patients with a history of HBV infection, a hepatitis B core antibody test should be conducted at screening. If positive, hepatitis B DNA testing will be performed and if active HBV infection is ruled out, the patient may be eligible. b) Patients who are HCV antibody positive with undetectable HCV viral load may be eligible.\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- Has received a live vaccine within 30 days prior to randomization.\n- Known or severe (≥ Grade 3) hypersensitivity or allergy to sacituzumab govitecan and/or the chemotherapy regimen of choice in the TPC arm (eg, nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin), their metabolites, or formulation excipient.\n- Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.1.\n- Patients may not have received systemic anticancer treatment (with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment. Patients must have recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent at the time of study entry. Note: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study. Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.\n- Patients may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Patients participating in observational studies are eligible.\n- Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.\n- Have an active second malignancy. Note: patients with a history of malignancy that has been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, non-melanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.\n- Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate (with the exception of those treated with chemotherapy) provided they have stable CNS disease (defined as radiographic stability demonstrated with a minimum of 2 posttreatment brain imaging assessments; one performed during screening) for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability.\n- Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c) New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction of < 40%."}

Primary endpoints

• {"endpoint_text":"- PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death (whichever comes first).","definition_or_measurement_approach":"Time from randomization to objective progressive disease (PD) or death, whichever occurs first; assessed by Blinded Independent Central Review (BICR) per RECIST Version 1.1."}

Secondary endpoints

• {"endpoint_text":"- OS is defined as the time from the date of randomization until death due to any cause.","definition_or_measurement_approach":"Time from randomization until death from any cause."}
• {"endpoint_text":"- ORR is defined as the proportion of patients who achieve a CR or PR that is confirmed at least 4 weeks after initial documentation of response as assessed by BICR per RECIST Version 1.1.","definition_or_measurement_approach":"Proportion of patients with confirmed complete response (CR) or partial response (PR) confirmed ≥4 weeks after initial documentation, assessed by BICR per RECIST v1.1."}
• {"endpoint_text":"- DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive PD or death from any cause (whichever comes first) as assessed by BICR per RECIST Version 1.1.","definition_or_measurement_approach":"Time from first documentation of CR or PR to definitive PD or death, whichever occurs first; assessed by BICR per RECIST v1.1."}
• {"endpoint_text":"- TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR per RECIST Version 1.1.","definition_or_measurement_approach":"Time from randomization to first documentation of CR or PR; assessed by BICR per RECIST v1.1."}
• {"endpoint_text":"- Incidence of treatment-emergent AEs (TEAEs) and clinical laboratory abnormalities.","definition_or_measurement_approach":"Frequency and incidence of TEAEs and clinical laboratory abnormalities as recorded during treatment and follow-up."}
• {"endpoint_text":"- Mean change from baseline in the physical functioning domain of the EORTC QLQ-C30 at Week 25","definition_or_measurement_approach":"Mean change from baseline in the EORTC QLQ-C30 physical functioning domain score at Week 25."}
• {"endpoint_text":"- TTD of fatigue domain of the EORTC QLQ-C30 is defined as the time between the date of randomization and the date of assessment at which a patient experienced a deterioration (ie, ≥ 10 points worsening from baseline in the fatigue domain) or death","definition_or_measurement_approach":"Time from randomization to first assessment showing deterioration in the EORTC QLQ-C30 fatigue domain (≥10 point worsening from baseline) or death."}

Primary sponsor

Full Name

Gilead Sciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Signant Health Global LLC

Responsibilities

Patient reported outcome services and IXRS (patient-reported outcomes and interactive voice/web response system)

Name

Bioclinica Inc.

Responsibilities

Imaging Core Laboratory

Name

Labcorp Central Laboratory Services LP

Responsibilities

Central laboratory services

Name

Omnitrace Corp.

Responsibilities

Lost to Follow Up (LTFU) service

Third parties

• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Signant Health is providing patient reported outcome services and equipment for the study","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Provides Interactive Voice/Web Response System (IXRS) services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging Core Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"OmniTrace is a Lost to Follow Up (LTFU) service.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central Laboratory for the study","organisation_type":"Pharmaceutical company"}