Phase 3 Randomized Study of Sacituzumab Govitecan vs. Docetaxel in Advanced/Metastatic NSCLC Post-Platinum Chemotherapy and Anti-PD-1/PD-L1 Therapy
- Trial ID
- 2024-512148-50-00
- Protocol
- GS-US-577-6153
- Sponsor
- Gilead Sciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **overall survival (OS)** of patients with advanced or metastatic **non-small cell lung cancer (NSCLC)** treated with sacituzumab govitecan (SG) versus docetaxel. This comparison is clinically relevant as it aims to determine the efficacy of SG, a novel antibody-drug conjugate, in improving survival outcomes in a patient population that has progressed on or after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
Secondary objectives include:
- Comparing the effect of SG versus docetaxel on progression-free survival (PFS) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
- Evaluating the overall response rate (ORR) as assessed by the investigator per RECIST Version 1.1.
- Assessing the duration of response (DOR) as assessed by the investigator per RECIST Version 1.1.
- Determining the disease control rate (DCR) as assessed by the investigator per RECIST Version 1.1.
- Evaluating the safety and tolerability of the treatments.
- Assessing the quality of life (QOL) using the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ).
Participants
The clinical trial involves a total of **197 participants** diagnosed with **non-small cell lung cancer** (NSCLC). The study population includes both male and female subjects, aged 18 years and older, who are capable of providing informed consent. Participants are required to have a life expectancy of at least three months and must have progressed after prior treatment with platinum-based chemotherapy in combination with or sequentially with anti-PD-1/PD-L1 antibody. The trial includes individuals with documented Stage 4 NSCLC, as per the American Joint Committee on Cancer, Eighth Edition. Participants must have adequate hepatic and renal function, as well as measurable disease based on CT or MRI. The selection criteria also require an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Both genders are included, and the trial does not exclude vulnerable populations. The selection process ensures that participants meet specific health criteria, including adequate hematologic counts and the absence of transfusional or growth factor support within two weeks of study drug initiation. The trial does not specify any particular lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as an open-label, global, multicenter, randomized, Phase 3 study comparing **sacituzumab govitecan** versus **docetaxel** in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have experienced progression following platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. The primary objective is to compare overall survival (OS) between the two treatment groups. The trial is expected to conclude by February 20, 2025, with recruitment having commenced on February 18, 2022.
The trial employs a randomized, controlled design to ensure unbiased comparison between the two treatment arms. Participants will be randomly assigned to receive either sacituzumab govitecan or docetaxel, both administered via **intravenous use**. The maximum treatment period for each cycle is 21 days, with the dosing regimen for docetaxel set at a maximum of 75 mg/kg and for sacituzumab govitecan at a maximum of 20 mg/kg.
Study visits are structured to include an initial screening visit, where eligibility criteria are assessed, followed by regular follow-up visits to monitor treatment response and safety. The inclusion visit involves comprehensive assessments, including hepatic function tests, creatinine clearance, and confirmation of NSCLC stage and progression. Follow-up visits will evaluate primary and secondary endpoints, such as progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), as well as the incidence of treatment-emergent adverse events (TEAEs).
The end-of-study visit will occur upon completion of the treatment cycles or upon early termination. Participants are expected to remain in the study for the duration of the treatment cycles unless conditions necessitate early withdrawal, such as significant adverse events, disease progression, or withdrawal of consent. The trial's design ensures rigorous monitoring and data collection to achieve its objectives and provide valuable insights into the comparative efficacy and safety of the investigational treatments.
Treatment
The clinical trial involves the administration of two experimental medications: **Docetaxel Accord** and **Trodelvy**. **Docetaxel Accord** is a concentrate for solution for infusion, containing the active substance **docetaxel**. It is classified as an antineoplastic agent and is administered intravenously. The dosage is set at a maximum of 75 mg/kg per day, with a total maximum dose of 75 mg/kg over a treatment period of 21 days. The pharmaceutical form is a solution for infusion, and it is manufactured by Accord Healthcare S.L.U. Compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol.
**Trodelvy** is a powder for concentrate for solution for infusion, containing the active substance **sacituzumab govitecan**. It is categorized as an antibody drug conjugate and is also administered intravenously. The maximum daily dose is 10 mg/kg, with a total maximum dose of 20 mg/kg over a 21-day treatment period. The pharmaceutical form is a solution for infusion, and it is produced by Gilead Sciences Ireland Unlimited Company. Participant compliance is closely monitored to maintain the integrity of the dosing regimen.
In this study, **Docetaxel Accord** serves as the comparator treatment, while **Trodelvy** is the test treatment. Both medications are administered under controlled conditions to patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have experienced progression following platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. The primary objective of the trial is to compare the overall survival (OS) between the two treatment groups. No additional non-experimental treatments, such as placebo, are utilized in this study.
Efficacy
Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **Overall Survival (OS)**, defined as the time from the date of randomization until death due to any cause in the Intent-to-Treat (ITT) Analysis Set. Secondary endpoints include **Progression-Free Survival (PFS)**, which measures the time from randomization until objective disease progression or death, and **Objective Response Rate (ORR)**, defined as the proportion of patients achieving a complete response (CR) or partial response (PR) confirmed at least four weeks later. Additionally, **Duration of Response (DOR)** is assessed from the first documentation of CR or PR to the first documentation of progressive disease (PD) or death. **Disease Control Rate (DCR)** is also evaluated, representing the proportion of patients achieving CR, PR, or stable disease (SD).
Other secondary endpoints include the incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities, as well as the time to first deterioration in the shortness of breath domain and total score as measured by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ). Efficacy assessments will be conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, as assessed by the investigator. The schedule for measuring these parameters will be aligned with the trial protocol, ensuring consistent and accurate data collection throughout the study duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal [ULN], aspartate aminotransferase and alanine aminotransferase ≤ 2.5 ULN or ≤ 5 ULN if known liver metastases, and serum albumin > 3 g/dL). • Note: The investigator should follow local practice guidelines and/or the docetaxel label approved in the country of drug administration for assessing eligibility of patients for the study.
- Creatinine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976}.
- Participants assigned male at birth and participants assigned female patientsat birth of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 11.4.
- Participants assigned female at birth or participants assigned male at birth 18 years of age or older, able to understand and give written informed consent
- Life expectancy of 3 months or more
- Pathologically documented NSCLC with documented evidence of Stage 4 NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
- EGFR, ALK, and PD-L1 results are required prior to enrollment (see Section 6.3.10). Resulting for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment. For participants with squamous cell carcinoma, EGFR and ALK testing is optional.
- Must have progressed after platinum-based chemotherapy in combination with anti- PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially. • Note: Includes patients who received prior platinum-based chemoradiotherapy (with or without maintenance anti-PD-1/PD-L1 antibody) for Stage 3 disease. To be considered to have progressed during or after prior treatment with platinum-based chemotherapy, patients should have either received prior platinum-based chemotherapy in the recurrent/ metastatic setting or have experienced disease progression within 6 months of last dose of platinum-based chemotherapy administered as part of concurrent chemoradiation for Stage 3 disease or as neoadjuvant or adjuvant therapy. To be considered to have progressed during or after prior treatment with an anti-PD-1/PD-L1 antibody, patients should have either received this therapy in the recurrent/metastatic setting or have experienced disease progression during “maintenance” treatment following concurrent chemoradiation for Stage 3 disease. a) No additional treatments are allowed in the recurrent/metastatic setting for patients with no actionable genomic alterations. b) Patients with EGFR, ALK, or any other known actionable genomic alterations must have also received treatment with at least 1 locally approved and available TKI appropriate to the genomic alteration (see Appendix 8). c) Documented radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
- Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator in accordance with per RECIST Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (Appendix 11.6) before randomization
- Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1500/mm3, and platelets ≥ 100,000/μL).
Exclusion Criteria
- Patients who meet any of the following exclusion criteria at screening/Day −1 are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted): Mixed small-cell lung cancer and NSCLC histology.
- Clinically 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.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease 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 are taking 10 mg/day or less of prednisone or its equivalent. All participants with carcinomatous meningitis are excluded regardless of clinical stability.
- 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 left ventricular ejection fraction of less than 40%
- Active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months of enrollment
- Active serious infection requiring antibiotics.
- Positive HIV-1 or HIV-2 antibody with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
- Positive for hepatitis B surface antigen. Participants who test positive for hepatitis B core antibody will require hepatitis B virus DNA by quantitative polymerase chain reaction for confirmation of active disease.
- Positive hepatitis C antibody and detectable hepatitis C viral load.
- 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.
- Positive serum pregnancy test (Appendix 11.4) or participants assigned female at birth who are lactating.
- Known hypersensitivity to the study drugs, their metabolites, or formulation excipients.
- Requirement for ongoing therapy with or prior use of any prohibited medications for SG and docetaxel as per Sections 5.7.1 and 5.12, respectively.
- Received a prior anticancer biologic agent within 4 weeks prior to enrollment or have received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, > Grade 2 is considered not recovered) from AEs at the time of study entry.Participants participating in observational studies are eligible.
- Previously received treatment with any of the following: a) Topoisomerase 1 inhibitors. Any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase 1 b) Trop-2-targeted therapy c) Docetaxel as monotherapy or in combination with other agents
- NSCLC that is eligible for definitive local therapy alone.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 18 Feb 2022 | 7 |
 Belgium | Not Recruiting | 18 Feb 2022 | 12 |
 France | Not Recruiting | 18 Feb 2022 | 105 |
 Germany | Not Recruiting | 18 Feb 2022 | 25 |
 Greece | Not Recruiting | 18 Feb 2022 | 17 |
 Italy | Not Recruiting | 18 Feb 2022 | 27 |
 The Netherlands | Not Recruiting | 18 Feb 2022 | — |
 Poland | Not Recruiting | 18 Feb 2022 | 5 |
 Portugal | Not Recruiting | 18 Feb 2022 | 8 |
 Spain | Not Recruiting | 18 Feb 2022 | 130 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Docetaxel Accord 20 mg/1 ml concentrate for solution for infusion | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 75 | 21 | PRD3445550 |
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 10 | 21 | PRD9351384 |