A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy

Official Summary

The purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 418 participants

Study Arms

• Arm A: Lazertinib with Amivantamab SC-CF (EXPERIMENTAL)
  Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.
• Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion (EXPERIMENTAL)
  Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.

Interventions

• DRUG: Lazertinib — Lazertinib tablets will be administered orally.
• DRUG: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF) — Amivantamab injection will be administered subcutaneously by manual injection.
• DRUG: Amivantamab Intravenous — Amivantamab will be administered by IV infusion.

Primary Outcomes

• For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State (Pre-dose on Cycle 4 Day 1 (each cycle of 28 days))
• For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab (Pre-dose on Cycle 2 Day 1 (each cycle of 28 days))
• Area Under the Concentration (AUC) Time Curve of Amivantamab From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 2 (Cycle 2: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hours (hrs) post-dose on Day 1; Arm B: pre-infusion, end of infusion (EOI)+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1)

Secondary Outcomes

• Objective Response Rate (ORR) (Up to 3 years 4 months)
• Progression-Free Survival (PFS) (Up to 3 years 4 months)
• Duration of Response (DOR) (Up to 3 years 4 months)
• Time to Response (TTR) (Up to 3 years 4 months)
• Number of Participants With Adverse Events (AEs) (Up to 3 years 4 months)

Eligibility Criteria

Inclusion Criteria:

* Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by an Food and Drug Administration (FDA)-approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United Started \[US\]) or an accredited local laboratory (sites outside of the US)
* Have progressed on or after osimertinib (or another approved 3rd generation epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKI\]) and platinum-based chemotherapy (irrespective of order). a) The 3rd generation EGFR TKI must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. b) Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. c) Any adjuvant or neoadjuvant treatment, whether with a 3rd generation EGFR TKI or platinum based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease
* Have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) version 1.1
* Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
* Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia \[any grade\], Grade less than or equal to (\<=) 2 peripheral neuropathy, and Grade \<=2 hypothyroidism stable on hormone replacement)

Exclusion Criteria:

* Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors
* Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization
* Participant has symptomatic or progressive brain metastases
* Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
* Participant has uncontrolled tumor-related pain
* Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis

Trial Locations

• City of Hope Duarte, Duarte, California, United States
• City of Hope Orange County Lennar Foundation Cancer Center, Irvine, California, United States
• City of Hope Long Beach Elm, Long Beach, California, United States
• National Jewish Health, Denver, Colorado, United States
• Baptist Lynn Cancer Institute, Boca Raton, Florida, United States
• Orlando Health, Orlando, Florida, United States
• University of Kansas, Kansas City, Kansas, United States
• University of Michigan, Ann Arbor, Michigan, United States
• Astera Cancer Care, East Brunswick, New Jersey, United States
• Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States
• ...and 10 more locations

Study Officials

• Janssen Research & Development, LLC Clinical Trial — STUDY_DIRECTOR
  Janssen Research & Development, LLC

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