Collaborative Clinical-translational Cohort of Amivantamab Plus Lazertinib and Amivantamab Plus Chemotherapy in Patients With EGFR-mutant, Locally Advanced or Metastatic/Recurrent Non-Small Cell Lung Cancer (INSTAR Study)

NCT07507188 | Not Yet Recruiting Phase 2

• 1 other identifier: 4-2025-0569
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

• In this study, we hypothesized that immune engagement by amivantamab will enhance antitumor efficacy by modulating the immune microenvironment in combination with lazertinib in patients with untreated EGFR-mutant NSCLC or with chemotherapy (carboplatin plus pemetrexed) after progression with 3rd generation (3G) EGFR TKI.
• The primary objective of this study is to examine the patients' tumors for immunomodulatory effects of amivantamab-based regimens.
• In a phase 2, two cohort clinical trial, treatment naïve patients with EGFR-mutant NSCLC will be treated with amivantamab SC plus oral lazertinib (Cohort 1, n=30) or patients with EGFR-mutant NSCLC progressed on or after 3G EGFR TKI treated with amivantamab SC plus chemotherapy (Cohort 2, n=30).

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• • scRNA-seq and/or spatial RNA sequencing analysis. Multiplex IHC and/or FACS analysis.

  • Molecular candidates associated with the activity of amivantamab-based regimens identified by analyzing scRNA-seq and/or spatial RNA sequencing from pre-treatment tumor biopsy specimens and tumor tissue acquired at the time of C3D1. Multiplex IHC and/or FACS analysis performed either pre-treatment or post-treatment.

  through study completion, an average of 5 year

Secondary Outcomes (4)

• Objective Response rate (ORR)

  through study completion, an average of 5 year

• Progression-free survival (PFS)

  through study completion, an average of 5 year

• Duration of response (DoR)

  through study completion, an average of 5 year

• circulating tumor DNA (ctDNA).

  through study completion, an average of 5 year

Other Outcomes (2)

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (TRAE, Clinical laboratory test, Vital signs, Physical Examination, Weight)

  through study completion, an average of 5 year

• The biomarker and ctDNA samples.

  through study completion, an average of 5 year

Study Arms (2)

Cohort 1

EXPERIMENTAL

• No prior exposure to 1st, 2nd, or 3rd EGFR TKIs

Drug: Amivantamab SC + Lazertinib PO

Cohort 2

EXPERIMENTAL

• Disease progression after prior treatment with 3rd generation (3G) EGFR TKI (including osimertinib, lazertinib)

Drug: Amivantamab SC + Chemotherapy (Carboplatin IV & Pemetrexed IV)

Interventions

Amivantamab SC + Lazertinib PO DRUG

• Amivantamab SC plus Lazertinib PO: 28-day Cycles * Amivantamab 1600/2240 mg SC QW up to C2D1 and Q2W thereafter; * Lazertinib 240 mg PO QD

Cohort 1

Amivantamab SC + Chemotherapy (Carboplatin IV & Pemetrexed IV) DRUG

* Amivantamab SC plus Chemotherapy: 21-day Cycles 1-4 * Amivantamab 1600/2240 mg SC C1D1; 2400/3360 mg C1D8, C1D15, and Day 1 of Cycles 2, 3, 4 * Pemetrexced 500 mg/m2 IV Day 1 * Carboplatin AUC5 IV Day 1 * Amivantamab SC plus Chemotherapy: 21-day Cycles 5+ * Amivantamab 2400/3360 mg SC Day 1 * Pemetrexed 500 mg/m2 IV Day 1

Cohort 2

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older
• Provision of informed consent prior to any study specific procedures
• Histologically or cytologically confirmed Locally advanced, Recurrent, or Metastatic NSCLC, performed on a biopsy and able to do a paired biopsy during treatment (C3D1)
• Documented activating EGFR mutation (Exon 19 deletion or L858R)
• Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: ≤ grade 1
• Patient should meet following requirements.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN, (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels)
• Leukocytes ≥ 3.0 x 10\^3/μL
• Hemoglobin ≥ 9.0 g/dL, with no blood transfusions in the 28 days prior to study entry
• Absolute neutrophil count ≥ 1.5 x 10\^3/μL
• Platelets ≥ 75 x 10\^3/μL
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (details in Appendix 10. Cockcroft-Gault Formula for Estimated Creatinine Clearance) \>50 mL/min for patients with creatinine levels \>1.5 x upper limit above institutional normal

You may not qualify if:

• Leptomeningeal carcinomatosis or uncontrolled central nervous system (CNS) metastases
• Symptomatic spinal cord compression that has not been treated definitively with surgery or radiation
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• Patients who are known to be serologically positive for human immunodeficiency virus (HIV)
• Participant has concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Principal Investigator:
• Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured.
• Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
• Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
• Localized prostate cancer (N0M0):
• with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance,
• with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence,
• or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
• Breast cancer:
• \- lobular carcinoma in situ or ductal carcinoma in situ that is considered completely cured.
• Participant has undergone curative therapy and is considered cured after 5 years with no evidence of disease recurrence since initiation of that therapy.

Sponsors & Collaborators

• Yonsei University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

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

Study Record Dates

• First Submitted: March 8, 2026
• First Posted: April 2, 2026
• Study Start: April 6, 2026
• Primary Completion (Estimated): January 31, 2031
• Study Completion (Estimated): January 31, 2031
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share