Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The purpose of the study is to separately assess the potential of dexamethasone, montelukast and methotrexate administration, prior to amivantamab infusion given through a needle in the vein, to decrease the incidence and/or severity of first-dose infusion related reactions.
Interventions
DRUGDexamethasone
Dexamethasone will be administered orally.
DRUGMontelukast
Montelukast will be administered orally.
DRUGMethotrexate
Methotrexate will be administered subcutaneously.
DRUGAmivantamab
Amivantamab will be administered intravenously.
DRUGLazertinib
Lazertinib tablets will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have advanced or metastatic non-small cell lung cancer (NSCLC) * Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 * A female participant using oral contraceptives must use an additional barrier contraceptive method * A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment, oral lazertinib and intravenous (IV) Amivantamab * Each participant, or legally authorized representative, where allowed, must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study * Progressed on or after prior treatment with osimertinib and platinum-based chemotherapy. Prior use of first-or-second generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is allowed if administered prior to osimertinib * Previously identified EGFR-mutated non-small cell lung cancer (NSCLC) (EGFR Exon19 deletion or L858R) (identified locally in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified laboratory \[or equivalent\])
Exclusion criteria
* Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis * Prior treatment with anti PD-1 or anti PD-L1 antibody within 6 weeks of planned first dose of study treatment or immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment * Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have completed definitive therapy, are not on steroids, and have a stable clinical status for at least 2 weeks prior to study treatment are allowed. If brain metastases are diagnosed on Screening imaging, the participant may be enrolled, or rescreened for eligibility, after definitive treatment if above criteria are met * 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 therapy) * Prior treatment with amivantamab or lazertinib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | Cycle 1 Day 1 (each cycle of 28 days) | Percentage of participants with IRRs at Cycle 1 Day 1 was reported. IRRs were defined as IRR events with onset time within 24 hours of the start of the first amivantamab infusion and prior to the start of amivantamab infusion on Cycle 1 Day 2. IRR included chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever. IRRs that occurred on Cycle 1 Day 2 pre-infusion were considered under Cycle 1 Day 1. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events of Infusion-related Reactions (IRRs) During Cycle 1 Day 1 | Cycle 1 Day 1 (each cycle of 28 days) |
| Percentage of Participants With Adverse Events (AEs) of Infusion-related Reactions (IRRs) as Per Severity up to End of Cycle 3 (Cycle 3 Day 28) | From Cycle 1 Day 1 up to Cycle 3 Day 28 (each cycle of 28 days) |
| Percentage of Participants With IRRs up to End of Treatment (EOT) | From Cycle 1 Day 1 (each cycle of 28 days) up to 27.3 months |
| Percentage of Participants With Other Adverse Events (AEs): Non-IRRs | From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months |
| Duration of Infusion Time for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1 | Cycle 1 Day 1 (each cycle of 28 days) |
| Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1 | Up to 4 hours on Cycle 1 Day 1 (each cycle of 28 days) |
| Overall Response Rate (ORR) | From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months |
| Duration of Response (DOR) | From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months |
Countries
France, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Dexamethasone 4 Milligrams (mg) Participants were administered with oral dexamethasone 4 mg tablet as a prophylactic treatment twice a day (8 mg total daily dose) on Day -1 (Cycle 1) prior to combination therapy of lazertinib 240 mg oral tablets and IV infusion of amivantamab 1050 mg (for participants less than \[\<\] 80 kilograms \[kg\]) or 1400 mg (for participants greater than or equal to \[\>=\] 80 kg) on Cycle 1 Day 1 until disease progression or withdrawal from study. Each cycle was of 28 days. | 6 |
| Cohort A2: Dexamethasone 8 mg Participants were administered with oral dexamethasone 8 mg tablet as a prophylactic treatment twice a day (16 mg total daily dose) on Day -2 and -1 (Cycle 1) and 8 mg approximately one hour prior to IV infusion of amivantamab 1050 mg (for participants \<80 kg) or 1400 mg (for participants \>=80 kg) on Cycle 1 Day 1 until disease progression or withdrawal from study. Each cycle was of 28 days. | 41 |
| Cohort B: Montelukast 10 mg Participants were administered with oral montelukast 10 mg tablet as a prophylactic treatment once daily in the morning on Days - 4, -3, -2, -1, and Cycle 1 Day 1 prior to combination therapy of lazertinib 240 mg oral tablets and IV infusion of amivantamab 1050 mg (for participants \<80 kg) or 1400 mg (for participants \>=80 kg) on Cycle 1 Day 1 until disease progression or withdrawal from study. Each cycle was of 28 days. | 15 |
| Cohort C: Methotrexate 25 mg Participants were administered with a single dose of methotrexate 25 mg subcutaneous injection as a prophylactic treatment on any day between Days -7 and Day -3 (Cycle 1) prior to combination therapy of lazertinib 240 mg oral tablets and IV infusion of amivantamab 1050 mg (for participants \<80 kg) or 1400 mg (for participants \>=80 kg) on Cycle 1 Day 1 until disease progression or withdrawal from study. Each cycle was of 28 days. | 6 |
| Total | 68 |
Baseline characteristics
| Characteristic | Cohort A: Dexamethasone 4 Milligrams (mg) | Cohort A2: Dexamethasone 8 mg | Cohort B: Montelukast 10 mg | Cohort C: Methotrexate 25 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 13.6 | 62.0 years STANDARD_DEVIATION 9.68 | 65.0 years STANDARD_DEVIATION 8.72 | 66.2 years STANDARD_DEVIATION 11.96 | 62.7 years STANDARD_DEVIATION 10.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 31 Participants | 13 Participants | 6 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 8 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 24 Participants | 10 Participants | 6 Participants | 42 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 4 Participants | 0 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 26 Participants | 10 Participants | 5 Participants | 44 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 5 Participants | 1 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 4 / 41 | 2 / 15 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 41 / 41 | 15 / 15 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 20 / 41 | 5 / 15 | 2 / 6 |
Outcome results
Primary
Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1
Percentage of participants with IRRs at Cycle 1 Day 1 was reported. IRRs were defined as IRR events with onset time within 24 hours of the start of the first amivantamab infusion and prior to the start of amivantamab infusion on Cycle 1 Day 2. IRR included chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever. IRRs that occurred on Cycle 1 Day 2 pre-infusion were considered under Cycle 1 Day 1.
Time frame: Cycle 1 Day 1 (each cycle of 28 days)
Population: The per protocol analysis set included all participants who had received all prophylaxis treatment based on schedule and had received the administration of amivantamab and lazertinib on Cycle 1 Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Dexamethasone 4 Milligrams (mg) | Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | 83.3 Percentage of participants |
| Cohort A2: Dexamethasone 8 mg | Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | 22.5 Percentage of participants |
| Cohort B: Montelukast 10 mg | Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | 66.7 Percentage of participants |
| Cohort C: Methotrexate 25 mg | Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | 83.3 Percentage of participants |
Secondary
Duration of Infusion Time for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle of 28 days)
Secondary
Duration of Response (DOR)
Time frame: From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months
Secondary
Overall Response Rate (ORR)
Time frame: From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months
Secondary
Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1
Time frame: Up to 4 hours on Cycle 1 Day 1 (each cycle of 28 days)
Secondary
Percentage of Participants With Adverse Events (AEs) of Infusion-related Reactions (IRRs) as Per Severity up to End of Cycle 3 (Cycle 3 Day 28)
Time frame: From Cycle 1 Day 1 up to Cycle 3 Day 28 (each cycle of 28 days)
Secondary
Percentage of Participants With Adverse Events of Infusion-related Reactions (IRRs) During Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle of 28 days)
Secondary
Percentage of Participants With IRRs up to End of Treatment (EOT)
Time frame: From Cycle 1 Day 1 (each cycle of 28 days) up to 27.3 months
Secondary
Percentage of Participants With Other Adverse Events (AEs): Non-IRRs
Time frame: From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months