A Study of Amivantamab and Lazertinib in People With Non-Small Cell Lung Cancer (NSCLC)

NCT04965090 | Completed Phase 2 FDA Drug

• 1 other identifier: 21-144
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers think that the study drugs, amivantamab and lazertinib, may be an effective treatment for people who have metastatic NSCLC with an EGFR mutation. Both drugs work to target cancer cells with an EGFR mutation, and this targeting action could stop or slow the growth of cancer cells. The researchers are doing this study to find out how well amivantamab and lazertinib work against metastatic NSCLC with an EGFR mutation.

Conditions

Recurrent Non Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer

Keywords

Amivantamab; Lazertinib; Metastatic EGFR-mutant Lung Cancer; CNS Metastases; 21-144

Outcome Measures

Primary Outcomes (2)

• CNS overall response rate (ORR) (Cohort 1)

  Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients with EGFR-mutant lung cancer with progressive or new parenchymal brain metastases. RANO-BM will be used when 5-9MM and RECIST 1.1 when 1cm or greater.

  2 years

• measure CNS overall response rate (ORR) (Cohort 2)

  Per modified Response Assessment in Neuro-Oncology (RANO-LM) and systemic ORR by RECIST v1.1 in patients with EGFR-mutant lung cancer and progressive or new leptomeningeal disease

  2 years

Study Arms (2)

Patients with parenchymal brain metastases

EXPERIMENTAL

All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh \<80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.

Drug: Amivantamab; Drug: Lazertinib

Patients with leptomeningeal (LM) disease with or without parenchymal brain metastases

EXPERIMENTAL

All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh \<80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.

Drug: Amivantamab; Drug: Lazertinib

Interventions

Amivantamab DRUG

Amivantamab 1050mg IV once weekly for the first 28 days (Cycle 1) and every other week thereafter. For subjects who weigh ≥80 kg, they will receive 350mg IV on C1D1 and 1050 mg on C1D2. They will continue to receive amivantamab 1400 IV once weekly for the first 28 days and every other week thereafter. Each cycle is 28 days in length.

Patients with leptomeningeal (LM) disease with or without parenchymal brain metastases; Patients with parenchymal brain metastases

Lazertinib DRUG

Lazertinib 240 mg orally once daily and take this continuously, starting C1D1. For patients who weigh \<80 kg, on C1D1, patients will receive amivantamab 350 mg IV, with 700 mg given on C1D2.

Patients with leptomeningeal (LM) disease with or without parenchymal brain metastases; Patients with parenchymal brain metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Written informed consent
• Advanced biopsy-proven metastatic or recurrent non-small cell lung cancer
• Somatic activating mutation in EGFR in a prior tumor biopsy or cfDNA sample
• Patients will have progressed on standard of care therapies
• Patients with EGFR exon 20 insertions will have progressed on platinum-based chemotherapy
• Patients with EGFR alterations sensitizing to tyrosine kinase inhibitors (TKIs) will have progressed on osimertinib
• Patients will be allowed to have received other systemic therapies since progression on the above, including investigational agents at least 28 days or 5 half lives prior to the first dose of study drug, whichever is shorter
• Subjects must have at least one measurable (at least 5 mm) intracranial metastasis lesion. For lesions ≥5 mm and \<10 mm RANO-BM will be used. For Lesions \> 10 mm (1cm) RECIST 1.1 criteria will be used.
• For Cohort A, subjects must have new or progressing CNS metastases. Extracranial measurable disease is not required.
• For Cohort B, subjects must have evidence of LM involvement by positive CSF cytology or presence of CTCs in CSF. Extracranial measurable disease is not required.
• Recent extracranial tissue biopsy within 8 weeks of C1D1 or willingness to undergo a repeat tumor biopsy. If subjects do not have an extracranial lesion amenable to biopsy, this requirement may be waived.
• Karnofsky performance status (KPS) ≥60%
• Ability to swallow oral medications
• Adequate organ function

You may not qualify if:

• Pregnant or lactating women
• Any radiotherapy within 1 week of starting treatment on protocol
• Any major surgery within 1 week of starting treatment on protocol
• Clinically significant toxicities from previous treatment
• Previous systemic chemotherapy within 2 weeks of starting treatment on protocol
• EGFR TKI or other oral treatment within 3 days of starting treatment on protocol
• Interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis requiring prolonged steroids or other immune suppressive agents that is unresolved or resolved within the last 3 months
• Progressive neurological symptoms requiring escalating doses of steroids or not controlled with steroids
• Positive hepatitis B (hepatitis B virus \[HBV\]) surface antigen (HBsAg)
• NOTE: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Patients who fit these criteria must use Hep B prophylaxis during treatment. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing
• Positive hepatitis C antibody (anti-HCV)
• NOTE: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible
• Other clinically active or chronic liver disease
• Participant is positive for human immunodeficiency virus (HIV), with 1 or more of the following:
• Receiving ART that may interfere with study treatment (consult sponsor for review of medication prior to enrollment)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Chen MF, Lee JJ, Choudhury NJ, Hui AB, Jeng MY, Zheng J, Aly RG, Sielski N, Ahn L, Pupo A, Nesselbush MC, Jabara I, Wilcox JA, Santomasso BD, Lin AL, Schaff L, Chaft JE, Riely GJ, Kris MG, Arfe A, Yang SR, Young RJ, Diehn M, Boire A, Yu HA. Phase 2 Study of Amivantamab Plus Lazertinib in Previously Treated Patients With EGFR-Mutant Lung Cancers With Brain and Leptomeningeal Metastases. J Thorac Oncol. 2026 Mar;21(3):103505. doi: 10.1016/j.jtho.2025.10.012. Epub 2025 Oct 23.

  PMID: 41139066 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

amivantamab; lazertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Helena Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 16, 2021
• Study Start: September 30, 2021
• Primary Completion: December 15, 2025
• Study Completion: December 15, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)