A Study of Lazertinib with Subcutaneous Amivantamab Compared with Intravenous Amivantamab in Participants with Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer

JRCT ID: jRCT2041220053

Registered date:13/08/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced or Metastatic Non-Small Cell Lung Cancer
• Date of first enrollment: 07/11/2022
• Target sample size: 418
• Countries of recruitment: Argentina,Japan,Brazil,Japan,Canada,Japan,China,Japan,Spain,Japan,France,Japan,Israel,Japan,Italy,Japan,Malaysia,Japan,Poland,Japan,Turkey,Japan,Taiwan,Japan,United States Of America,Japan,Australia,Japan,Germany,Japan,United Kingdom Of Great Britain,Japan,Korea,Republic Of,Japan,Portugal,Japan
• Study type: Interventional

Intervention(s)

Arm A: Lazertinib with Amivantamab SC-CF
- Lazertinib 240 milligrams (mg) will be administered orally once daily.
- Participants will receive Amivantamab subcutaneous and coformulated 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
- 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.

Outcome(s)

Primary Outcome

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 on Cycle 4 Day 1
Cycle 4 Day 1 (28 days cycle)
Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.

For EU and Any Applicable Region:
Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1
Cycle 2 Day 1 (28 days cycle)
Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.

Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2
Cycle 2 Day 1 to Cycle 2 Day 15 (28 days cycle)
AUC(Day 1-15) defined as area under the concentration time curve from Cycle2 Day 1 to Day 15, will be reported.

Secondary Outcome

Objective Response Rate (ORR)
Up to 1 year 11 months
ORR is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1).

Progression-Free Survival (PFS)
Up to 1 year 11 months
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1.

Duration of Response (DOR)
Up to 1 year 11 months
The DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.

Time to Response(TTR).
Up to 1 year 11 months
Time to response (that is time to first response) is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, as defined by BICR using RECIST version 1.1., for participants who have PR or CR as their best response.

Number of Participants With Adverse Events (AEs)
Up to 4 year 11 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is
obtained.

Number of Participants with AEs by Severity
Up to 4 year 11 months
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. This outcome includes participants continuing in the LTE
Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.

Number of Participants with Clinical Laboratory Abnormalities
Up to 4 year 11 months
Number of participants with clinical laboratory abnormalities (serum Chemistry, hematology, coagulation and urinalysis) will be reported. This outcome includes participants continuing in the LTE Phase
for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.

Number of Participants with Clinical Laboratory Abnormalities by Severity
Up to 4 year 11 months
Number of participants with clinical laboratory abnormalities by severity (serum Chemistry, hematology, coagulation and urinalysis) will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4=Life-threatening and Grade 5= Death related to adverse event. This outcome includes participants continuing in the LTE Phase for whom, after the primary analysis, data were collected until a discontinuation criterion is met, or until 3 years after local marketing authorization is obtained.

Number of Participants Infusion Related Reactions (IRRs)
Up to 1 year 11 months
Number of participants with IRRs will be reported.

Number of Participants with Infusion Related Reactions (IRRs) by Severity
Up to 1 year 11 months
Number of participants with IRRs by severity will be reported.

For All Regions Other Than the EU and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1
Cycle 2 Day 1 (28 days cycle)
The Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2
Day 1 immediately prior to the next drug administration.

For EU and Any Applicable Region:Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle4 Day 1
Cycle 4 Day 1 (28 days cycle)
The Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.

Model-Predicted Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab at Steady State of Cycle 4
From Cycle 4 Day 1 to Cycle 4 Day 15 (28 days cycle)
Model-predicted AUC(Day 1-15) defined as area under the concentration time curve from Cycle 4 Day 1 to Day 15, will be reported.

Percentage of Participants with Presence of Antiamivantamab Antibodies and Anti-rHuPH20 Antibodies
Up to 1 year 11 months
Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.

Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)
Up to 1 year 11 months
Percentage of participants with cancer therapy satisfaction in will be assessed using the modified TASQ. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.

Change from Baseline in TASQ as Assessed Over Time
Up to 1 year 11 months
Change from baseline in TASQ as assessed Over time will be reported. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.

Participant Chair Time
Up to 1 year 11 months
Participant chair time will be assessed by time and motion analysis.

Duration of Treatment Administration
Up to 1 year 11 months
Duration of treatment administration will be assessed by time and motion analysis.

Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring.
Up to 1 year 11 months
Active health care professional time for drug preparation, treatment administration, and posttreatment monitoring will be assessed by time and motion analysis.

Participant Time in Treatment Room
Up to 1 year 11 months
Participant time in treatment room will be assessed by time and motion analysis.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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)

Exclude 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

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): NCT05388669,2024-512045-16-00