Phase 2 Evaluation of AMG 193 Efficacy and Safety in MTAP-Deleted Advanced Non-Small Cell Lung Cancer

The primary objective of this Phase 2 study is to **characterize the safety and efficacy** of two dose levels of AMG 193 in subjects with Methylthioadenosine Phosphorylase (MTAP)-deleted previously treated advanced **Non-Small Cell Lung Cancer** (NSCLC). This evaluation is conducted by the investigator in Part 1 and by Blinded Independent Central Review (BICR) in both Part 1 and Part 2. The clinical relevance of this objective lies in determining the potential of AMG 193 as a therapeutic option for this specific patient population, which could lead to improved treatment outcomes.

Secondary objectives include:

• Evaluating other measures of AMG 193 anti-tumor activity by BICR and by the investigator.
• Assessing **Overall Survival** (OS).
• Evaluating the safety and tolerability of AMG 193.
• Evaluating the pharmacokinetics (PK) of AMG 193.
• Exploring the subject experience with AMG 193 treatment using subject-reported outcome instruments.

The clinical trial involves a total of **104 participants** diagnosed with **Non-Small Cell Lung Cancer**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on specific criteria, including a histologically or cytologically confirmed diagnosis of metastatic or unresectable locally advanced MTAP-deleted non-small cell lung cancer. All participants have previously received and progressed on at least one prior systemic therapy for their condition. The trial does not include vulnerable populations. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria require participants to have a life expectancy of greater than three months and allow for those with treated brain metastases or untreated asymptomatic brain metastases under certain conditions. The selection process ensures that participants meet these criteria to evaluate the safety and efficacy of AMG 193.

The clinical trial is a **Phase 2** study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of **AMG 193** in subjects with **Methylthioadenosine Phosphorylase (MTAP)-deleted** previously treated advanced **Non-Small Cell Lung Cancer (NSCLC)**. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial extends from the recruitment start date on April 23, 2025, to the estimated end date on December 31, 2028.

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 confirmed metastatic or unresectable locally advanced MTAP-deleted NSCLC, prior systemic therapy, and a life expectancy of greater than three months. The study will include follow-up visits to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will conclude the trial for each participant, assessing the primary and secondary endpoints, including objective response, incidence of treatment-emergent adverse events, and pharmacokinetic parameters.

The expected length of participant involvement will vary depending on individual response and progression, with the maximum treatment period set at 9999 days. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent by the participant. The trial aims to provide comprehensive data on the efficacy and safety of AMG 193, contributing to the understanding and potential treatment options for advanced NSCLC.

The clinical trial involves the administration of **AMG 193**, an investigational antineoplastic agent developed by Amgen Inc. **AMG 193** is formulated as a tablet for oral administration. The active substance, also named **AMG 193**, is of chemical origin. The trial aims to evaluate the efficacy, safety, tolerability, and pharmacokinetics of this compound in subjects with Methylthioadenosine Phosphorylase (MTAP)-deleted previously treated advanced non-small cell lung cancer (NSCLC). The study will assess two dose levels of **AMG 193**. The specific dosage, frequency of administration, and maximum daily dose are not explicitly defined in the provided data, indicating that these parameters may be determined based on the study's progression and participant response. The maximum treatment period is set at 9999 days, suggesting a long-term evaluation of the treatment's effects.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the monotherapy efficacy of **AMG 193**. Participant compliance with the dosing schedule will be monitored throughout the study to ensure accurate assessment of the drug's effects. The trial's main objective is to characterize the safety and efficacy of **AMG 193** by investigator assessment in Part 1 and by Blinded Independent Central Review (BICR) in both Part 1 and Part 2 of the study.

The efficacy of AMG 193 in the treatment of advanced non-small cell lung cancer (NSCLC) with **Methylthioadenosine Phosphorylase (MTAP)** deletion will be assessed through several primary and secondary endpoints. The primary endpoints include the objective response (OR), which encompasses complete response (CR) and partial response (PR), as measured by computed tomography (CT) or magnetic resonance imaging (MRI) and evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Additionally, the incidence of treatment-emergent adverse events (TEAEs), grade ≥ 3 TEAEs, serious adverse events (SAEs), and events of interest (EOIs) will be monitored. Pharmacokinetic (PK) parameters of AMG 193, such as maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC), will also be evaluated.

Secondary endpoints will include disease control (DC), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and overall survival (OS). The incidence and severity of TEAEs, grade ≥ 3 TEAEs, SAEs, and EOIs will be further assessed. Changes in cancer-specific symptoms, treatment-related symptoms, and overall health status will be measured using subject-reported outcome instruments, including EORTC QLQ-C30, QLQ LC13, EQ-5D-5L, PRO-CTCAE, and GP5 of FACT-G. These assessments will provide a comprehensive evaluation of the efficacy and safety profile of AMG 193 in this patient population.