Efficacy of Durvalumab and Tremelimumab as Consolidation Therapy in Limited Stage Small-Cell Lung Cancer Post-Concurrent Chemoradiation Therapy

The primary objective of this Phase III, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of **durvalumab** monotherapy compared to placebo in patients with Limited Stage Small-Cell Lung Cancer (LS-SCLC) who have not progressed following concurrent chemoradiation therapy. The primary endpoints are progression-free survival (PFS) and overall survival (OS), which are critical measures of treatment effectiveness in prolonging life and delaying disease progression in this patient population.

Secondary objectives include assessing the efficacy of the combination of **durvalumab** and **tremelimumab** versus placebo in terms of PFS and OS. Additionally, the study aims to evaluate the efficacy of durvalumab monotherapy and the durvalumab and tremelimumab combination versus placebo in terms of overall response rate (ORR), PFS at 18 and 24 months, time to distant metastasis (TTDM), OS at 24 and 36 months, and PFS2. The study also compares the efficacy of the durvalumab and tremelimumab combination versus durvalumab monotherapy in terms of PFS, ORR, and OS. Furthermore, the study investigates disease-related symptoms and health-related quality of life (HRQoL) using the EORTC QLQ-C30 v3 and QLQ-LC13 questionnaires, pharmacokinetics (PK) of the treatments, safety and tolerability, immunogenicity, and the relationship between PD-L1 expression and spatial distribution for the therapies.

The clinical trial involves a total of **562 participants** diagnosed with **Limited Stage Small-Cell Lung Cancer (LS-SCLC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific inclusion criteria, including a histologically or cytologically confirmed diagnosis of limited-stage SCLC, and having completed a first-line concurrent chemoradiotherapy regimen. The trial population is characterized by a World Health Organization/Eastern Cooperative Oncology Group performance status of 0 or 1, indicating a generally good health status. Lifestyle considerations such as diet and physical activity are not specified, but the trial does include a vulnerable population. The selection process ensures that participants have not progressed following definitive, platinum-based chemotherapy concurrent with radiotherapy. The trial aims to assess the efficacy of durvalumab monotherapy compared to placebo in terms of progression-free survival (PFS) and overall survival (OS).

The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, multi-center, international study designed to evaluate the efficacy of **durvalumab** and **tremelimumab** as consolidation treatments for patients with limited-stage small-cell lung cancer (LS-SCLC) who have not progressed following concurrent chemoradiation therapy. The trial aims to assess the efficacy of durvalumab monotherapy compared to placebo in terms of progression-free survival (PFS) and overall survival (OS). The study is expected to commence recruitment on June 3, 2024, and conclude by March 5, 2026, with a maximum treatment period of 24 months for participants.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically or cytologically documented LS-SCLC, completion of a platinum-based chemotherapy regimen, and a WHO/ECOG performance status of 0 or 1. Following the screening, eligible participants will be randomized to receive either durvalumab, durvalumab with tremelimumab, or a placebo. The trial includes regular follow-up visits to monitor safety, efficacy, and any adverse events, with assessments conducted according to RECIST 1.1 criteria. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

The expected length of participant involvement is up to 24 months, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. The trial will also evaluate secondary endpoints such as objective response rate (ORR), PFS at 18 and 24 months, time to distant metastasis (TTDM), and quality of life assessments using EORTC QLQ-C30 and QLQ-LC13. Safety assessments will include monitoring adverse events, laboratory findings, and vital signs. The study will also explore the presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab, and the expression of PD-L1 in tumor and immune cells relative to response and efficacy outcomes.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Mycophenolate mofetil** is provided in the form of capsules and is administered orally. It is classified as an immunosuppressive agent. The specific dosage and frequency of administration are not detailed in the provided data, but the treatment period is set for a maximum of 24 months.

**Infliximab** is administered as a powder for concentrate for solution for infusion, delivered intravenously. It is categorized as a protein-based treatment. The maximum treatment period is also 24 months, with specific dosing details not provided in the data.

**Tremelimumab**, marketed as IMJUDO, is provided as a 20 mg/ml concentrate for solution for infusion. It is administered intravenously, with a maximum daily dose of 75 mg and a total dose of 75 mg over the treatment period. The treatment duration is up to 24 months.

**Dextrose BP** is used as a placebo in this study. It is administered as a solution for infusion intravenously. The treatment period is up to 24 months, with no specific dosing information provided.

**Sodium chloride** is another placebo used in the trial, administered as a solution for infusion intravenously. The treatment period is up to 24 months, with no specific dosing information available.

**Durvalumab**, marketed as IMFINZI, is provided as a 50 mg/mL concentrate for solution for infusion. It is administered intravenously, with a maximum daily dose of 1500 mg and a total dose of 1500 mg over the treatment period. The treatment duration is up to 24 months.

Participant compliance with the dosing schedule is monitored throughout the trial, although specific methods of compliance monitoring are not detailed in the provided data. The trial aims to assess the efficacy of durvalumab monotherapy compared to placebo in terms of progression-free survival (PFS) and overall survival (OS) in patients with limited-stage small-cell lung cancer who have not progressed following concurrent chemoradiation therapy.

The efficacy of the clinical trial will be assessed by comparing the effects of **durvalumab** monotherapy to placebo in patients with limited-stage small-cell lung cancer (SCLC) who have not progressed following concurrent chemoradiation therapy. The primary endpoints for evaluating efficacy include progression-free survival (PFS) and overall survival (OS), as determined by blinded independent central review (BICR) assessments according to RECIST 1.1 criteria. Secondary endpoints will further explore PFS, overall response rate (ORR), PFS at 18 and 24 months, time to distant metastasis (TTDM), and additional OS metrics at 24 and 36 months. Patient-reported outcomes will be measured using the EORTC QLQ-C30 and QLQ-LC13 questionnaires to assess changes in symptoms, functioning, and global health status/quality of life (QoL).

Additional secondary endpoints include the concentration of durvalumab and tremelimumab in serum, presence of anti-drug antibodies (ADA), and PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes. Safety assessments will be conducted through monitoring adverse events (AEs), laboratory findings, physical examinations, vital signs, and electrocardiograms. The trial is designed as a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study, with an estimated end date in March 2026. The trial will adhere to a structured schedule for measuring and collecting data at specified timepoints throughout the study duration.