Phase II Dose Selection Study of Intravenous BI 764532 in Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer and Neuroendocrine Carcinomas

The primary objective of this trial is to evaluate the **safety** and efficacy of two dose levels of BI 764532 monotherapy in patients with Small Cell Lung Cancer (SCLC) who have experienced progression or recurrence following at least two prior lines of therapy, including at least one platinum-based regimen. Additionally, the study targets patients with histologically or cytologically confirmed advanced or metastatic extra-pulmonary neuroendocrine carcinoma (epNEC), excluding Merkel cell carcinoma (MCC), medullary thyroid carcinoma (MTC), and neuroendocrine prostate cancer (NEPC), or large cell neuroendocrine carcinoma (LCNEC) of the lung, as defined by the 2022 WHO classification of Neuroendocrine Neoplasms, who have had progression or recurrence following at least one platinum-based regimen. This evaluation is clinically relevant as it aims to address the unmet need for effective treatments in these patient populations, who have limited therapeutic options after standard treatments fail.

The secondary objectives include further evaluation of the efficacy of BI 764532 monotherapy by assessing the duration of objective response (DOR), disease control (DC), progression-free survival (PFS) by investigator assessment, and overall survival (OS). The study also aims to explore the effect of BI 764532 on core patient-reported outcomes (PROs) and to further assess the safety and tolerability of BI 764532 monotherapy. These secondary objectives are crucial for understanding the broader impact of the treatment on patient quality of life and long-term outcomes.

The clinical trial involves a total of **64 participants** diagnosed with **Small Cell Lung Cancer** (SCLC), extra-pulmonary neuroendocrine carcinoma (epNEC), or large cell neuroendocrine carcinoma (LCNEC) of the lung. The study population includes both male and female participants aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants were selected based on their progression or recurrence following at least two prior lines of therapy for SCLC, including one platinum-based regimen, or at least one platinum-based regimen for epNEC or LCNEC. The trial population is characterized by a requirement for measurable lesions as per RECIST v1.1 and adequate organ function. Lifestyle considerations such as diet and physical activity are not specified, but participants must have resolved toxicities from previous therapies to ≤ CTCAE Grade 1, except for certain conditions. Both genders are included, and the trial involves a vulnerable population, necessitating informed consent and adherence to effective birth control methods for participants of childbearing potential.

The clinical trial is designed to evaluate the **safety** and **efficacy** of two dose levels of BI 764532 monotherapy in patients with **Small Cell Lung Cancer** (SCLC) and other neuroendocrine carcinomas. This is a Phase II, open-label, multi-center trial involving patients who have experienced progression or recurrence following at least two prior lines of therapy, including one platinum-based regimen. The trial employs a randomized, controlled design to ensure robust data collection and analysis. The estimated duration of the trial is from October 2023 to July 2025, with participant involvement expected to last up to 36 weeks, depending on individual response and tolerance to the treatment.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, cancer type, and previous treatment history. This visit will include assessments of **ECOG performance status**, measurable lesions, and organ function. Following successful screening, participants will receive the investigational product, BI 764532, administered as a **solution for infusion** via **intravenous infusion**. Subsequent follow-up visits will occur regularly to monitor treatment response, adverse events, and overall health status. These visits will include tumor assessments according to RECIST v1.1, laboratory tests, and patient-reported outcomes.

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination include disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision based on clinical judgment. Primary endpoints include objective response and the occurrence of treatment-emergent adverse events, while secondary endpoints focus on duration of response, progression-free survival, disease control, overall survival, and patient-reported outcomes. The trial aims to provide valuable insights into the potential benefits and risks of BI 764532 for patients with challenging neuroendocrine malignancies.

The clinical trial involves the administration of **BI 764532**, an investigational medication developed by Boehringer Ingelheim International. This medication is formulated as a **solution for infusion** and is administered via **intravenous infusion**. The active substance in BI 764532 is a **protein** of biological origin, specifically an **IgG-like T cell engager** that targets DLL3 and CD3. The maximum daily dose of BI 764532 is 60 mg, with a total maximum dose of 3120 mg over a treatment period of up to 36 weeks. The trial aims to evaluate the safety and efficacy of two dose levels of BI 764532 monotherapy in patients with relapsed or refractory extensive-stage small cell lung cancer (SCLC) and other neuroendocrine carcinomas.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of BI 764532. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial is designed to assess the therapeutic potential of BI 764532 in a specific patient population, with careful monitoring of safety and efficacy outcomes.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Objective Response (OR)**, defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 by investigator assessment, and the occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period. Secondary endpoints encompass the **Duration of Objective Response (DOR)**, which is the time from first documented confirmed OR until the earliest date of disease progression or death among patients with confirmed OR, and **Progression-Free Survival (PFS)**, defined as the time from treatment start until the earliest date of tumor progression according to RECIST v 1.1 or death from any cause. Additionally, **Disease Control (DC)**, defined as the best overall response of CR, PR, or stable disease (SD) based on investigator assessment, and **Overall Survival (OS)**, defined as the time from treatment start until death from any cause, will be evaluated. Patient-reported outcomes (PRO) will also be assessed, including changes from baseline in EORTC QLQ-C30 physical and role functioning domain scores. The occurrence of treatment-emergent adverse events leading to study drug discontinuation during the on-treatment period will also be monitored. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, with analysis conducted according to the predefined criteria and methodologies outlined in the trial protocol.