Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
EGFR Exon20ins Mutation, NSCLC
Brief summary
The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.
Interventions
DRUGAmivantamab
Amivantamab will be administered as an IV infusion at a dose of 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3 and will continue the same treatment in OLE phase then in LTE phase.
DRUGPemetrexed
Pemetrexed will be administered as 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arm A and will continue the same treatment in OLE phase then in LTE phase.
DRUGCarboplatin
Carboplatin will be administered as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.
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
* Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation * Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream * A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
Exclusion criteria
* Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance) * Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible) * Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation * Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis * Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) | From randomization to either disease progression or death whichever occurs first (up to 29 months) | PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) in the absence of progression, whichever came first. Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment. Pharmacodynamic: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Anti-Amivantamab Antibodies | Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1) |
| Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | From baseline to 5 years 3 months |
| Objective Response Rate (ORR) | Up to 5 years 3 months |
| Duration of Response (DoR) | Up to 5 years 3 months |
| Overall Survival (OS) | Up to 5 years 3 months |
| Time to Subsequent Therapy (TST) | Up to 5 years 3 months |
| Progression-Free Survival After First Subsequent Therapy (PFS2) | Up to 5 years 3 months |
| Time to Symptomatic Progression (TTSP) | Up to 5 years 3 months |
| Number of Participants Treatment-emergent Adverse Events (TEAEs) | From Day 1 to 5 years 2 months |
| Number of Participants TEAEs With Severity | From Day 1 to 5 years 2 months |
| Number of Participants With Clinical Laboratory Abnormalities | Up to 5 years 3 months |
| Number of Participants With Vital Signs Abnormalities | Up to 5 years 3 months |
| Number of Participants With Physical Examination Abnormalities | Up to 5 years 3 months |
| Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) | From baseline to 5 years 3 months |
| Serum Concentration of Amivantamab | Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1) |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Poland, Portugal, Puerto Rico, Russia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Currently, the results are posted till cut-off date 03-May-2023. After completion of open-label extension (OLE) phase participant were allowed to enter the long-term extension (LTE) phase. LTE phase is still ongoing and results will be posted upon study completion.
Participants by arm
| Arm | Count |
|---|---|
| Arm B: Chemotherapy Alone Participants received chemotherapy with pemetrexed 500 milligrams per meter square (mg/m\^2) Intraveous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 (AUC 5) IV infusion administered on Day 1 for up to 4 cycles, and then as maintenance monotherapy until disease progression. Following the primary analysis, the study was transitioned to an open-label extension (OLE) phase, and participants either continued to receive the chemotherapy or crossover to amivantamab in the OLE phase. | 155 |
| Arm A: Amivantamab + Chemotherapy Participants received amivantamab 1400 milligrams (mg) (1750 mg if body weight is greater than or equal to (\>=) 80 kilograms \[kg\]) by IV infusion once weekly starting from Cycle 1 Day 1 up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3 up to Cycle 5 Day 1. Participants received chemotherapy with pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 milligrams per milliliter (mg/mL) per minute (AUC 5) was administered as an IV infusion on Day 1, for up to 4 cycles, and then as maintenance monotherapy until disease progression. Following the primary analysis, the study was transitioned to an OLE phase, and participants continued to receive amivantamab plus chemotherapy in the OLE phase. | 153 |
| Total | 308 |
Baseline characteristics
| Characteristic | Arm A: Amivantamab + Chemotherapy | Total | Arm B: Chemotherapy Alone |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 11.92 | 59.6 years STANDARD_DEVIATION 11.95 | 60 years STANDARD_DEVIATION 12.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 22 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 282 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 97 Participants | 186 Participants | 89 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 49 Participants | 109 Participants | 60 Participants |
| Region of Enrollment AUSTRALIA | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment BELGIUM | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment BRAZIL | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment CANADA | 5 Participants | 8 Participants | 3 Participants |
| Region of Enrollment CHINA | 39 Participants | 87 Participants | 48 Participants |
| Region of Enrollment FRANCE | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment GERMANY | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment HUNGARY | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment INDIA | 5 Participants | 11 Participants | 6 Participants |
| Region of Enrollment ISRAEL | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment ITALY | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment JAPAN | 19 Participants | 34 Participants | 15 Participants |
| Region of Enrollment MALAYSIA | 10 Participants | 11 Participants | 1 Participants |
| Region of Enrollment MEXICO | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment POLAND | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment PORTUGAL | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment SOUTH KOREA | 13 Participants | 23 Participants | 10 Participants |
| Region of Enrollment SPAIN | 16 Participants | 29 Participants | 13 Participants |
| Region of Enrollment TAIWAN | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment THAILAND | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment TURKEY | 3 Participants | 13 Participants | 10 Participants |
| Region of Enrollment UNITED KINGDOM | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment UNITED STATES | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 85 Participants | 178 Participants | 93 Participants |
| Sex: Female, Male Male | 68 Participants | 130 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 42 / 155 | 28 / 151 |
| other Total, other adverse events | 149 / 155 | 151 / 151 |
| serious Total, serious adverse events | 48 / 155 | 56 / 151 |
Outcome results
Primary
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) in the absence of progression, whichever came first. Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment. Pharmacodynamic: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).
Time frame: From randomization to either disease progression or death whichever occurs first (up to 29 months)
Population: Full analysis set included all randomized participants, classified according to their assigned treatment arm regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Chemotherapy Alone | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) | 6.70 Months |
| Arm A: Amivantamab + Chemotherapy | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) | 11.37 Months |
p-value: <0.000195% CI: [0.296, 0.528]Log Rank
Secondary
Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Time frame: From baseline to 5 years 3 months
Secondary
Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)
Time frame: From baseline to 5 years 3 months
Secondary
Duration of Response (DoR)
Time frame: Up to 5 years 3 months
Secondary
Number of Participants TEAEs With Severity
Time frame: From Day 1 to 5 years 2 months
Secondary
Number of Participants Treatment-emergent Adverse Events (TEAEs)
Time frame: From Day 1 to 5 years 2 months
Secondary
Number of Participants With Anti-Amivantamab Antibodies
Time frame: Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Secondary
Number of Participants With Clinical Laboratory Abnormalities
Time frame: Up to 5 years 3 months
Secondary
Number of Participants With Physical Examination Abnormalities
Time frame: Up to 5 years 3 months
Secondary
Number of Participants With Vital Signs Abnormalities
Time frame: Up to 5 years 3 months
Secondary
Objective Response Rate (ORR)
Time frame: Up to 5 years 3 months
Secondary
Overall Survival (OS)
Time frame: Up to 5 years 3 months
Secondary
Progression-Free Survival After First Subsequent Therapy (PFS2)
Time frame: Up to 5 years 3 months
Secondary
Serum Concentration of Amivantamab
Time frame: Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Secondary
Time to Subsequent Therapy (TST)
Time frame: Up to 5 years 3 months
Secondary
Time to Symptomatic Progression (TTSP)
Time frame: Up to 5 years 3 months