Advanced or Metastatic Non-small Cell Lung Cancer
Conditions
Brief 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.
Interventions
DRUGLazertinib
Lazertinib tablets will be administered orally.
Amivantamab injection will be administered subcutaneously by manual injection.
Amivantamab will be administered by IV infusion.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Ctrough was the observed serum concentration of Amivantamab at steady state immediately prior to the next drug administration. |
| For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab | Pre-dose on Cycle 2 Day 1 (each cycle of 28 days) | Ctrough was the observed serum concentration of Amivantamab immediately prior to the next drug administration. |
| 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 | AUC (Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15 were reported. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Number of Participants With AEs by Severity | Up to 3 years 4 months |
| Number of Participants With Clinical Laboratory Abnormalities | Up to 3 years 4 months |
| Number of Participants With Clinical Laboratory Abnormalities by Severity | Up to 3 years 4 months |
| Number of Participants With Infusion Related Reactions (IRRs) | Up to 3 years 4 months |
| Number of Participants With IRRs by Severity | Up to 3 years 4 months |
| 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 | Pre-dose on Cycle 2 Day 1 (each cycle of 28 days) |
| For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1 | Pre-dose on Cycle 4 Day 1 (each cycle of 28 days) |
| Model-Predicted Area Under the Concentration Time Curve of Amivantamab at Steady State From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 4 | Cycle 4: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hrs post-dose on Day 1; Arm B: preinfusion, EOI+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1 |
| Percentage of Participants With Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies | Up to 3 years 4 months |
| Percentage of Participants With Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ) | Up to 3 years 4 months |
| Change From Baseline in Therapy Administration Satisfaction Questionnaire (TASQ) as Assessed Over Time | From baseline (Day 1, Cycle 1) to 3 years 4 months (each cycle of 28 days) |
| Participant Chair Time | Up to 3 years 4 months |
| Participant Chair Time in Treatment Room | Up to 3 years 4 months |
| Duration of Treatment Administration | Up to 3 years 4 months |
| Active Health Care Professional (HCP) Time For Drug Preparation, Treatment Administration and Post-treatment Monitoring | Up to 3 years 4 months |
Countries
Argentina, Australia, Brazil, Canada, China, France, Germany, Israel, Italy, Japan, Malaysia, Poland, Portugal, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
The results are currently reported for primary analysis till clinical cut-off date 03-Jan-2024. Upon completion of the open-label follow-up phase, participants were permitted to enter the long-term extension (LTE) phase. The LTE phase is ongoing and results will be published after the completion of the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 10.25 |
| Age, Customized 50-64 years | 196 Participants |
| Age, Customized <50 years | 57 Participants |
| Age, Customized 65-74 years | 125 Participants |
| Age, Customized >=75 years | 40 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 129 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 155 Participants |
| Region of Enrollment Argentina | 5 Participants |
| Region of Enrollment Australia | 17 Participants |
| Region of Enrollment Brazil | 6 Participants |
| Region of Enrollment Canada | 18 Participants |
| Region of Enrollment China | 47 Participants |
| Region of Enrollment France | 4 Participants |
| Region of Enrollment Germany | 5 Participants |
| Region of Enrollment Israel | 4 Participants |
| Region of Enrollment Italy | 27 Participants |
| Region of Enrollment Japan | 56 Participants |
| Region of Enrollment Korea, South | 41 Participants |
| Region of Enrollment Malaysia | 9 Participants |
| Region of Enrollment Poland | 0 Participants |
| Region of Enrollment Portugal | 5 Participants |
| Region of Enrollment Spain | 15 Participants |
| Region of Enrollment Taiwan | 6 Participants |
| Region of Enrollment Thailand | 2 Participants |
| Region of Enrollment Turkey | 2 Participants |
| Region of Enrollment United Kingdom | 2 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 138 Participants |
| Sex: Female, Male Male | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 43 / 206 | 61 / 210 |
| other Total, other adverse events | 201 / 206 | 207 / 210 |
| serious Total, serious adverse events | 59 / 206 | 64 / 210 |
Outcome results
None listed