A Phase 3 Randomized Study of Lazertinib and Subcutaneous Amivantamab Versus Intravenous Amivantamab in EGFR-Mutated Advanced NSCLC Post-Osimertinib and Chemotherapy

The primary objective of this Phase 3, open-label, randomized study is to assess the **noninferiority** of subcutaneous amivantamab administered via manual injection compared to intravenous amivantamab in patients with **EGFR-mutated advanced or metastatic non-small cell lung cancer** who have experienced progression following treatment with osimertinib and chemotherapy. This evaluation is clinically relevant as it may offer a more convenient administration route for patients, potentially improving adherence and quality of life without compromising efficacy.

The clinical trial involves a total of **342 participants** diagnosed with **EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, such as having histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer with specific EGFR mutations, and having progressed on or after treatment with osimertinib or another approved third-generation EGFR tyrosine kinase inhibitor and platinum-based chemotherapy. The trial does not include a vulnerable population. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to assess the noninferiority of amivantamab administered subcutaneously via manual injection compared to intravenous administration.

The clinical trial is designed to evaluate the **noninferiority** of subcutaneous administration of **amivantamab** compared to its intravenous administration in patients with **EGFR-mutated advanced or metastatic non-small cell lung cancer**. This is a Phase 3, open-label, randomized study involving two arms: Arm A, where participants receive subcutaneous amivantamab, and Arm B, where participants receive intravenous amivantamab. The trial also includes the administration of **lazertinib** in tablet form. The study is expected to run from September 2022 to August 2025, with the primary endpoint being the **Ctrough** of amivantamab at steady state, specifically on Cycle 4 Day 1 for most regions, and Cycle 2 Day 1 for the EU and other applicable regions.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as confirmed **EGFR** mutations and progression after prior treatments. Follow-up visits will occur at regular intervals to monitor the drug's pharmacokinetics and participants' health status. The end-of-study visit will conclude the trial, assessing the overall outcomes and any adverse events. The expected length of participant involvement is approximately 28 days per treatment cycle, with multiple cycles anticipated throughout the study duration.

Participants may be subject to early termination from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial's design ensures rigorous monitoring and data collection to achieve its primary objective of assessing the noninferiority of the subcutaneous route compared to the intravenous route of amivantamab administration.

The clinical trial involves the administration of **amivantamab** in two different pharmaceutical forms. The first form is a **solution for injection** under the product code JNJ-61186372. This formulation is administered via **subcutaneous use**. The active substance, amivantamab, is a protein-based therapeutic agent. The dosing schedule for this formulation is determined by the study protocol, with a maximum treatment period of 28 days. Participant compliance is monitored through regular assessments and documentation of administration.

The second form of amivantamab is a **solution for infusion**, also under the product code JNJ-61186372. This formulation is administered via **intravenous use**. Similar to the subcutaneous form, the active substance is amivantamab, and it is also protein-based. The dosing schedule and maximum treatment period are consistent with the subcutaneous formulation, with compliance monitoring in place to ensure adherence to the protocol.

Additionally, the trial includes the administration of **lazertinib**, a chemical-based therapeutic agent, under the product code JNJ-73841937. Lazertinib is provided in **tablet** form and is administered via **oral use**. The dosing schedule for lazertinib is aligned with the study's protocol, with a maximum treatment period of 28 days. Compliance with the oral administration is monitored through participant self-reporting and pill counts during study visits.

Throughout the trial, the administration of these medications is carefully documented, and participant adherence to the dosing schedules is closely monitored to ensure the integrity of the study data. The trial aims to assess the noninferiority of subcutaneous amivantamab compared to intravenous administration in patients with **EGFR-mutated advanced or metastatic non-small cell lung cancer** following progression on osimertinib and chemotherapy.

The efficacy of the investigational treatments in this clinical trial will be assessed using specific **pharmacokinetic** parameters as primary endpoints. These include the **Ctrough** of **amivantamab** at steady state, measured on Cycle 4 Day 1 for all regions except the EU, where it will be assessed on Cycle 2 Day 1 and pre-dose on Cycle 2 Day 1. Additionally, the **AUCD1-D15** in Cycle 2 will be evaluated. These parameters will be collected and analyzed to determine the noninferiority of subcutaneous administration of amivantamab compared to its intravenous administration in patients with EGFR-mutated advanced or metastatic non-small cell lung cancer who have progressed after treatment with osimertinib and chemotherapy.