A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination with Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination with Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The primary objective is to assess the antitumor activity of **amivantamab** in combination with **lazertinib** in **EGFR-mutated** **non-small cell lung cancer** patient populations. This evaluation is clinically relevant for determining the efficacy of this combination therapy in patients with common EGFR mutations who have **locally advanced** or **metastatic** disease, addressing treatment needs in both **first-line** and **second-line** settings where **platinum-based chemotherapy** may also be utilized.

The clinical trial enrolled a total of **354 participants** diagnosed with common **EGFR-mutated locally advanced or metastatic non-small cell lung cancer**. The study population included both **male and female subjects** comprising **adults** and **elderly individuals**. Participants were selected based on histologically or cytologically confirmed advanced or metastatic disease not amenable to curative intent therapy. Eligible subjects were required to have specific **EGFR mutations**, including **exon 19 deletion** or **exon 21 L858R substitution**, confirmed by validated testing in certified or accredited laboratories. Key selection criteria included the presence of at least one measurable lesion according to **RECIST version 1.1** that had not been previously irradiated, resolution of prior treatment toxicities to **NCI-CTCAE version 5.0 grade 1** or baseline level with specific exceptions, and an **Eastern Cooperative Oncology Group performance status** of 0 to 1. The trial did not include vulnerable populations.

This is a Phase 2b, open-label, two-cohort study evaluating the efficacy and safety of subcutaneous **amivantamab** in combination with **lazertinib** as first-line treatment, or subcutaneous amivantamab in combination with platinum-based **chemotherapy** as second-line treatment, in adult participants with common **EGFR-mutated** locally advanced or **metastatic non-small cell lung cancer**. The study employs a non-randomized, open-label design where both participants and investigators are aware of the treatment assignment. The trial is designed to assess the antitumor activity of amivantamab in combination with lazertinib in this specific patient population.

The primary endpoint of the study is **progression-free survival** according to RECIST version 1.1 by investigator assessment. The study is estimated to commence recruitment in November 2025 and is expected to conclude by November 2030, representing an overall trial duration of approximately five years. The exact duration of individual participant involvement will depend on treatment response and tolerability.

Eligible participants must have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer that is not amenable to curative intent therapy. The **EGFR mutation** must be either an exon 19 deletion or exon 21 L858R substitution, as detected by FDA-approved or other validated test in a CLIA-certified laboratory in the United States, or an accredited local laboratory outside the United States. Participants must have at least one measurable lesion according to RECIST version 1.1 that has not been previously irradiated. Any toxicities from prior systemic anticancer therapy must have resolved to NCI-CTCAE version 5.0 grade 1 or baseline level, with exceptions for alopecia of any grade, grade 2 or lower peripheral neuropathy, or grade 2 or lower hypothyroidism stable on hormone replacement. An **Eastern Cooperative Oncology Group** performance status of 0 to 1 is required for study entry.

The investigational treatment consists of **JNJ-61186372** (amivantamab), administered as a solution for injection via subcutaneous route, in combination with **JNJ-73841937** (lazertinib), administered orally as a tablet. The active substances are amivantamab, a protein-based therapeutic agent, and lazertinib, a chemical compound. Study visits will include a screening visit to assess eligibility criteria, followed by regular treatment and assessment visits throughout the study period. Participants will undergo periodic evaluations to monitor disease progression, treatment response, and adverse events. An end-of-study visit will be conducted upon treatment discontinuation or study completion.

Participants may be withdrawn from the study under various conditions, including disease progression, unacceptable toxicity, withdrawal of consent, investigator decision, or administrative reasons. The maximum treatment period is defined as one cycle, though the specific duration of each cycle is determined by the study protocol. Treatment may continue beyond one cycle based on clinical benefit and tolerability assessments. The study follows standard oncology trial procedures with continuous monitoring for safety and efficacy throughout the participant's involvement in the trial.

The experimental treatment consists of two investigational medicinal products administered in combination. JNJ-73841937 contains the active substance lazertinib, which is of chemical origin. This investigational product is supplied as a tablet for oral use. JNJ-61186372 contains the active substance amivantamab, which is a protein-based substance. This investigational product is supplied as a solution for injection administered via subcutaneous use.

Both investigational medicinal products are classified as test products in this clinical trial. The study evaluates the antitumor activity of amivantamab in combination with lazertinib in patients with EGFR-mutated non-small cell lung cancer. The trial is designed as an open-label, two-cohort study investigating subcutaneous amivantamab in combination with lazertinib as first-line treatment, or subcutaneous amivantamab in combination with platinum-based chemotherapy as second-line treatment for common EGFR-mutated locally advanced or metastatic non-small cell lung cancer.

Neither investigational product represents a paediatric formulation. Both medicinal products are manufactured by JANSSEN-CILAG INTERNATIONAL N.V. The maximum treatment period for both investigational products is defined as one day, with dosing schedules and specific dosage information to be determined according to the study protocol requirements.

Efficacy will be assessed using progression-free survival (PFS) according to RECIST version 1.1 by investigator assessment as the primary endpoint. The evaluation will focus on the antitumor activity of amivantamab in combination with lazertinib in patients with EGFR-mutated non-small cell lung cancer. Participants must have at least one measurable lesion according to RECIST version 1.1 that has not been previously irradiated to allow for appropriate efficacy assessment throughout the trial.