Phase 3 Randomized Study of Sacituzumab Govitecan Versus Standard of Care in Previously Treated Extensive Stage Small Cell Lung Cancer

The primary objective of this study is to compare the effect of **sacituzumab govitecan** (SG) to standard of care (SOC) on the objective response rate (ORR) in patients with previously treated extensive stage small cell lung cancer (ES-SCLC). This is assessed by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Additionally, the study aims to compare the effect of SG to SOC on overall survival (OS). These objectives are clinically relevant as they address the efficacy of SG in improving response rates and survival outcomes in a challenging patient population with limited treatment options.

Secondary objectives include:

• Comparing the effect of SG to SOC on progression-free survival (PFS) as assessed by BICR according to RECIST v1.1.
• Comparing the effect of SG to SOC on duration of response (DOR) as assessed by BICR according to RECIST v1.1.
• Comparing the effect of SG to SOC on shortness of breath.
• Comparing the effect of SG to SOC on physical functioning.
• Comparing the safety and tolerability of SG to SOC.

The clinical trial involves a total of **453 participants** diagnosed with **Extensive Stage Small Cell Lung Cancer (ES-SCLC)**. The study population includes both male and female subjects, with an age range primarily between 18 to 64 years. Participants were selected based on a histologically confirmed diagnosis of SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. The trial includes individuals with measurable disease as determined by computed tomography (CT) or magnetic resonance imaging (MRI) and requires documentation of radiological disease progression following at least one prior line of platinum-containing chemotherapy. The trial population is inclusive of a vulnerable population, and lifestyle factors such as diet and physical activity are not specified. The selection criteria ensure that at least 85% of participants have been pretreated with anti-PD-[L]1 therapy. The study does not specify any particular lifestyle considerations or habits of the participants.

The clinical trial is a **randomized**, open-label, Phase 3 study designed to evaluate the efficacy of **sacituzumab govitecan** compared to the standard of care in participants with previously treated **extensive stage small cell lung cancer (ES-SCLC)**. The primary objectives are to assess the objective response rate (ORR) and overall survival (OS) as evaluated by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Secondary endpoints include progression-free survival (PFS), duration of response (DOR), time to first deterioration in shortness of breath and physical functioning, and the incidence of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities.

The trial is expected to commence recruitment on July 31, 2025, and is estimated to conclude by November 1, 2029. Participants will be involved in the study for a maximum treatment period of 21 days per cycle, with the possibility of multiple cycles depending on individual response and tolerance. The study will include an initial screening visit to confirm eligibility based on criteria such as a histologically confirmed diagnosis of SCLC, an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and measurable disease by CT or MRI. Participants must also have documented radiological disease progression after one prior line of platinum-containing chemotherapy.

Following the screening, participants will be randomized to receive either sacituzumab govitecan or the standard of care. Study visits will be scheduled regularly to monitor treatment response and safety, with assessments conducted according to RECIST v1.1 criteria. The end-of-study visit will occur after the final treatment cycle or upon early termination. Conditions that may lead to early termination include unacceptable toxicity, disease progression, or withdrawal of consent. The trial is not categorized as low intervention and is conducted in accordance with Regulation EU No 536/2014, with a deferral of public document release for five years post-trial or until marketing authorization is achieved.

The clinical trial involves the administration of two primary treatments: **HYCAMTIN** and **Trodelvy**. **HYCAMTIN** is a pharmaceutical product containing the active substance **topotecan**, which is classified as a chemical antineoplastic agent. It is provided in the form of a powder for concentrate for solution for infusion, specifically designed for intravenous administration. The maximum daily dose of **HYCAMTIN** is 2.3 mg/m², and the treatment period is set for a maximum of 21 days. The product is manufactured by Sandoz Pharmaceuticals D.D. and is authorized for use in the European Union under the marketing authorization number EU/1/96/027/003.

**Trodelvy**, on the other hand, contains the active substance **sacituzumab govitecan**, which is a protein-based antibody-drug conjugate. Similar to **HYCAMTIN**, **Trodelvy** is also provided as a powder for concentrate for solution for infusion and is administered intravenously. The maximum daily dose for **Trodelvy** is 12 mg/kg, with a treatment period also capped at 21 days. This product is manufactured by Gilead Sciences Ireland Unlimited Company and holds the marketing authorization number EU/1/21/1592/001 in the European Union.

In this trial, **Trodelvy** serves as the experimental treatment, while **HYCAMTIN** is used as the comparator treatment, representing the standard of care. Both treatments are administered under strict compliance monitoring to ensure adherence to dosing schedules and to evaluate the efficacy and safety of the experimental treatment in comparison to the standard therapy. The trial aims to assess the objective response rate and overall survival in participants with previously treated extensive-stage small cell lung cancer.

Efficacy in this clinical trial will be assessed using several key endpoints. The primary endpoints include the **Objective Response Rate (ORR)** and **Overall Survival (OS)**. ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as evaluated by a Blinded Independent Central Review (BICR) according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). OS is measured as the length of time from randomization until death from any cause.

Secondary endpoints include **Progression-Free Survival (PFS)**, **Duration of Response (DOR)**, time to first deterioration in shortness of breath, time to first deterioration in physical functioning, and the incidence of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities. PFS is defined as the time from randomization until disease progression as assessed by BICR according to RECIST v1.1 or death from any cause, whichever occurs first. DOR is measured from the time of first response (CR or PR) as assessed by BICR according to RECIST v1.1, until the date of first documented disease progression or death, whichever comes first.