Trial Outcomes & Findings for A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure (NCT NCT04988295)

Last Updated: 2025-11-13

Results Overview

PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: 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).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

776 participants

Primary outcome timeframe

From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months)

Results posted on

2025-11-13

Participant Flow

A total of 657 participants were enrolled in the main study. During the study, a separate open-label randomized extension cohort was added. A total of 119 participants were enrolled into the extension cohort. Main study results are alone reported for primary completion date (PCD; 10-July-2023).

At the time of PCD, extension cohort enrollment was still ongoing. As per protocol, extension cohort analysis was not included as part of main study primary analysis. Currently no information other than total count of participants for extension cohort is available and for reporting purpose extension cohort arms (A2 and C2) have been combined in the table. Results of extension cohort will be reported later, upon completion of analysis, at which point arms A2 and C2 details will be reported.

Participant milestones

Participant milestones
Measure	Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L) Schedule 1:LACP:study start to 06-Nov-2022:Lazertinib 240 milligrams(mg) orally daily along with amivantamab and chemotherapy (carboplatin and pemetrexed). Amivantamab 1400 mg (1750 mg if body weight\>= 80 kilograms\[kg\]) intravenous(IV) infusion on Cycle 1 Days 1/2, 8 and 15 and Cycle 2 Day 1 and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants received chemotherapy:pemetrexed 500 milligrams per meter square(mg/m\^2) IV infusion on Day 1 of each 21-day cycle, along with carboplatin area under concentration-time curve of 5 (AUC 5) IV infusion on Day 1 for up to 4 cycles and then as maintenance monotherapy until disease progression(DP). Schedule 2:ACP-L:07-Nov-2022 to study end:Amivantamab 1400 mg (1750 mg if body weight\>=80 kg) IV infusion on Cycle 1 Days 1/2, 8 and 15 and Cycle 2 Day 1 and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants also received chemotherapy:pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, along with carboplatin AUC 5 IV infusion on Day 1 for up to 4 cycles and then as maintenance monotherapy until DP. Lazertinib was administered 240 mg orally, once daily starting Cycle 5 Day 1 or sooner if carboplatin was discontinued earlier. In both schedules, Lazertinib, amivantamab and pemetrexed:continued until DP, participant withdrawal, adverse event, investigator's decision/initiation of new systemic anti-cancer treatment.	Main Study: Arm B: Carboplatin + Pemetrexed (CP) Participants received chemotherapy with pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 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, participant consent withdrawal, adverse event, investigator's decision, or initiation of new systemic anti-cancer treatment.	Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP) Participants received amivantamab 1400 mg (1750 mg if body weight is \>= 80 kg) by IV infusion once weekly starting from Cycle 1 Days 1/2, 8, and 15, and 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. Participants also received chemotherapy with pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 mg/mL per minute (AUC 5) was administered as an IV infusion on Day 1, for up to 4 cycles. Amivantamab and pemetrexed treatments were to be continued until disease progression, participant consent withdrawal, adverse event, investigator's decision, or initiation of new systemic anti-cancer treatment.	Extension Cohort: All Participants (Arm A2 [ACP-L] + C2 [ACP]) In Arm A2, participants received amivantamab 1400 mg (1750 mg if body weight\>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and Cycle 2 Day 1, and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under concentration-time curve of 5 mg/mL per minute (AUC 5) IV infusion administered on Day 1 for up to 4 cycles. Lazertinib was administered 240 mg orally, once daily starting Cycle 5 Day 1 or sooner if carboplatin was discontinued earlier. Amivantamab, pemetrexed and lazertinib were to be continued until disease progression (DP), participant withdrawal, adverse event (AE), investigator's decision or initiation of new systemic anti-cancer treatment. In Arm C2, participants received amivantamab 1400 mg (1750 mg if body weight \>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and 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. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin AUC 5 IV infusion was administered on Day 1, for up to 4 cycles. Amivantamab and pemetrexed were to be continued until DP, participant withdrawal, AE, investigator's decision or initiation of new systemic anti-cancer treatment.
Overall Study STARTED	263	263	131	119
Overall Study Treated (Safety Analysis Set)	263	243	130	119
Overall Study COMPLETED	67	65	26	0
Overall Study NOT COMPLETED	196	198	105	119

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L) Schedule 1:LACP:study start to 06-Nov-2022:Lazertinib 240 milligrams(mg) orally daily along with amivantamab and chemotherapy (carboplatin and pemetrexed). Amivantamab 1400 mg (1750 mg if body weight\>= 80 kilograms\[kg\]) intravenous(IV) infusion on Cycle 1 Days 1/2, 8 and 15 and Cycle 2 Day 1 and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants received chemotherapy:pemetrexed 500 milligrams per meter square(mg/m\^2) IV infusion on Day 1 of each 21-day cycle, along with carboplatin area under concentration-time curve of 5 (AUC 5) IV infusion on Day 1 for up to 4 cycles and then as maintenance monotherapy until disease progression(DP). Schedule 2:ACP-L:07-Nov-2022 to study end:Amivantamab 1400 mg (1750 mg if body weight\>=80 kg) IV infusion on Cycle 1 Days 1/2, 8 and 15 and Cycle 2 Day 1 and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants also received chemotherapy:pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, along with carboplatin AUC 5 IV infusion on Day 1 for up to 4 cycles and then as maintenance monotherapy until DP. Lazertinib was administered 240 mg orally, once daily starting Cycle 5 Day 1 or sooner if carboplatin was discontinued earlier. In both schedules, Lazertinib, amivantamab and pemetrexed:continued until DP, participant withdrawal, adverse event, investigator's decision/initiation of new systemic anti-cancer treatment.	Main Study: Arm B: Carboplatin + Pemetrexed (CP) Participants received chemotherapy with pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 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, participant consent withdrawal, adverse event, investigator's decision, or initiation of new systemic anti-cancer treatment.	Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP) Participants received amivantamab 1400 mg (1750 mg if body weight is \>= 80 kg) by IV infusion once weekly starting from Cycle 1 Days 1/2, 8, and 15, and 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. Participants also received chemotherapy with pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under the concentration-time curve of 5 mg/mL per minute (AUC 5) was administered as an IV infusion on Day 1, for up to 4 cycles. Amivantamab and pemetrexed treatments were to be continued until disease progression, participant consent withdrawal, adverse event, investigator's decision, or initiation of new systemic anti-cancer treatment.	Extension Cohort: All Participants (Arm A2 [ACP-L] + C2 [ACP]) In Arm A2, participants received amivantamab 1400 mg (1750 mg if body weight\>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and Cycle 2 Day 1, and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under concentration-time curve of 5 mg/mL per minute (AUC 5) IV infusion administered on Day 1 for up to 4 cycles. Lazertinib was administered 240 mg orally, once daily starting Cycle 5 Day 1 or sooner if carboplatin was discontinued earlier. Amivantamab, pemetrexed and lazertinib were to be continued until disease progression (DP), participant withdrawal, adverse event (AE), investigator's decision or initiation of new systemic anti-cancer treatment. In Arm C2, participants received amivantamab 1400 mg (1750 mg if body weight \>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and 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. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin AUC 5 IV infusion was administered on Day 1, for up to 4 cycles. Amivantamab and pemetrexed were to be continued until DP, participant withdrawal, AE, investigator's decision or initiation of new systemic anti-cancer treatment.
Overall Study Lost to Follow-up	1	0	0	0
Overall Study Withdrawal by Subject	9	29	6	0
Overall Study Study participation ongoing	186	169	99	119

Baseline Characteristics

For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L) n=263 Participants LACP dosing (study start until 6 November 2022): Participants received Lazertinib 240 milligrams (mg) orally on Day 1 of each subsequent cycle, starting with Cycle 3, along with Amivantamab 1400 mg (1750 mg if body weight greater than or equal to \[\>=80\] kilograms \[kg\]) on Cycle 1 Days 1, 2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg). Participant also received Pemetrexed 500 mg per square meter (mg/m\^2) on Day 1 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. From cycle 5 onwards, participants received Amivantamab, Pemetrexed and Lazertinib IV infusions at same dose, as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants received Amivantamab 1400 mg (1750 mg if body weight \>=80\] kg) on Cycle 1 Days 1,2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg). Participant also received Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. Lazertinib 240 mg in ACP-L started on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4. From cycle 5 onwards, participants received Amivantamab, Pemetrexed and Lazertinib IV infusions at same dose, as maintenance until disease progression. Each cycle consists of 21 days.	Main Study: Arm B: Carboplatin + Pemetrexed (CP) n=263 Participants Participants received Pemetrexed 500 mg/m\^2 IV infusion and carboplatin 750 mg IV infusion from Day 1 of Cycle 1 to 4. From cycle 5 onwards, participants received Pemetrexed 500 mg/m\^2 IV infusion, as maintenance until disease progression. Each cycle consists of 21 days.	Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP) n=131 Participants Participants received Amivantamab 1400 mg (1750 mg if body weight \>=80 kg) on Cycle 1 Days 1,2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each cycle, starting with Cycle 3. Participants also received Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. From cycle 5 onwards, participants received Amivantamab and Pemetrexed IV infusions at same dose, as maintenance until disease progression. Each cycle consists of 21 days.	Extension Cohort: All Participants (Arm A2 [ACP-L] + C2 [ACP]) In Arm A2, participants received amivantamab 1400 mg (1750 mg if body weight\>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and Cycle 2 Day 1, and then 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each 21-day cycle, starting at cycle 3. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin area under concentration-time curve of 5 mg/mL per minute (AUC 5) IV infusion administered on Day 1 for up to 4 cycles. Lazertinib was administered 240 mg orally, once daily starting Cycle 5 Day 1 or sooner if carboplatin was discontinued earlier. Amivantamab, pemetrexed and lazertinib were to be continued until disease progression (DP), participant withdrawal, adverse event (AE), investigator's decision or initiation of new systemic anti-cancer treatment. In Arm C2, participants received amivantamab 1400 mg (1750 mg if body weight \>=80 kg) IV infusion once weekly from Cycle 1 Days 1/2, 8, and 15, and 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. Participants also received chemotherapy: pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle, in combination with carboplatin AUC 5 IV infusion was administered on Day 1, for up to 4 cycles. Amivantamab and pemetrexed were to be continued until DP, participant withdrawal, AE, investigator's decision or initiation of new systemic anti-cancer treatment.	Total n=657 Participants Total of all reporting groups
Sex: Female, Male Female	168 Participants n=10 Participants	157 Participants n=10 Participants	81 Participants n=20 Participants	—	406 Participants n=44 Participants
Age, Continuous	60.3 years STANDARD_DEVIATION 10.96 • n=10 Participants	60.6 years STANDARD_DEVIATION 10.13 • n=10 Participants	61.2 years STANDARD_DEVIATION 10.06 • n=20 Participants	—	60.6 years STANDARD_DEVIATION 10.44 • n=44 Participants
Sex: Female, Male Male	95 Participants n=10 Participants	106 Participants n=10 Participants	50 Participants n=20 Participants	—	251 Participants n=44 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=10 Participants	23 Participants n=10 Participants	9 Participants n=20 Participants	—	54 Participants n=44 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	234 Participants n=10 Participants	234 Participants n=10 Participants	118 Participants n=20 Participants	—	586 Participants n=44 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=10 Participants	6 Participants n=10 Participants	4 Participants n=20 Participants	—	17 Participants n=44 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	3 Participants n=10 Participants	1 Participants n=20 Participants	—	4 Participants n=44 Participants
Race (NIH/OMB) Asian	125 Participants n=10 Participants	127 Participants n=10 Participants	63 Participants n=20 Participants	—	315 Participants n=44 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	—	0 Participants n=44 Participants
Race (NIH/OMB) Black or African American	4 Participants n=10 Participants	1 Participants n=10 Participants	3 Participants n=20 Participants	—	8 Participants n=44 Participants
Race (NIH/OMB) White	129 Participants n=10 Participants	123 Participants n=10 Participants	60 Participants n=20 Participants	—	312 Participants n=44 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	2 Participants n=10 Participants	0 Participants n=20 Participants	—	2 Participants n=44 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=10 Participants	7 Participants n=10 Participants	4 Participants n=20 Participants	—	16 Participants n=44 Participants
Region of Enrollment ARGENTINA	5 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	6 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	11 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment BELGIUM	10 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	3 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	3 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	16 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment BRAZIL	10 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	13 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	6 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	29 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment BULGARIA	0 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	2 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment CANADA	7 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	11 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	22 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment CHINA	45 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	40 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	15 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	100 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment CZECH REPUBLIC	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	3 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment FRANCE	14 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	18 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	7 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	39 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment GERMANY	3 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	7 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment HONG KONG	0 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	2 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	2 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment INDIA	14 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	8 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	26 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment ISRAEL	6 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	3 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	13 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment ITALY	20 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	19 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	11 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	50 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment JAPAN	17 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	24 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	9 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	50 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment MALAYSIA	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	5 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	8 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	17 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment MEXICO	5 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	2 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	11 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment NETHERLANDS	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	2 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	7 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment POLAND	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	9 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	14 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment PORTUGAL	4 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	2 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	7 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment RUSSIAN FEDERATION	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	1 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment SOUTH KOREA	25 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	21 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	17 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	63 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment SPAIN	30 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	24 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	13 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	67 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment SWEDEN	3 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	1 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	0 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	4 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment TAIWAN	10 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	17 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	7 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	34 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment TURKEY	10 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	5 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	4 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	19 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment UNITED KINGDOM	8 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	10 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	2 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	20 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.
Region of Enrollment UNITED STATES	9 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	7 Participants n=10 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	7 Participants n=20 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.	—	23 Participants n=44 Participants • For extension cohort, data was not available at the time of primary analysis results reporting. Hence, enrollment data was reported only for main study.

PRIMARY outcome

Timeframe: From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months)

Population: Full analysis set (FAS) as defined in the protocol included all randomized participants, classified according to their assigned treatment arm regardless of the actual treatment received. The outcomes reported here are for main study participants. For Arm A participants, data were planned to be analyzed as a single arm collectively for the LACP and ACP-L dosing regimens.

Outcome measures

Outcome measures
Measure	Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L) n=263 Participants LACP dosing (study start until 6 November 2022): Participants received Lazertinib 240 milligrams (mg) orally on Day 1 of each subsequent cycle, starting with Cycle 3, along with Amivantamab 1400 mg (1750 mg if body weight greater than or equal to \[\>=80\] kilograms \[kg\]) on Cycle 1 Days 1, 2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg). Participant also received Pemetrexed 500 mg per square meter (mg/m\^2) on Day 1 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. From cycle 5 onwards, participants received Amivantamab, Pemetrexed and Lazertinib IV infusions at same dose, as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants received Amivantamab 1400 mg (1750 mg if body weight \>=80\] kg) on Cycle 1 Days 1,2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg). Participant also received Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. Lazertinib 240 mg in ACP-L started on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4. From cycle 5 onwards, participants received Amivantamab, Pemetrexed and Lazertinib IV infusions at same dose, as maintenance until disease progression. Each cycle consists of 21 days.	Main Study: Arm B: Carboplatin + Pemetrexed (CP) n=263 Participants Participants received Pemetrexed 500 mg/m\^2 IV infusion and carboplatin 750 mg IV infusion from Day 1 of Cycle 1 to 4. From cycle 5 onwards, participants received Pemetrexed 500 mg/m\^2 IV infusion, as maintenance until disease progression. Each cycle consists of 21 days.	Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP) n=131 Participants Participants received Amivantamab 1400 mg (1750 mg if body weight \>=80 kg) on Cycle 1 Days 1,2, 8, and 15, and Cycle 2 Day 1 and 1750 mg (2100 mg if body weight \>=80 kg) on Day 1 of each cycle, starting with Cycle 3. Participants also received Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle, in combination with carboplatin 750 mg as IV infusion starting on Cycle 1 Day 1 for 4 cycles. From cycle 5 onwards, participants received Amivantamab and Pemetrexed IV infusions at same dose, as maintenance until disease progression. Each cycle consists of 21 days.
Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)	8.31 months Interval 6.77 to 9.1	4.17 months Interval 4.04 to 4.44	6.28 months Interval 5.55 to 8.41

PRIMARY outcome

Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L)

Serious events: 137 serious events

Other events: 261 other events

Deaths: 69 deaths

Main Study: Arm B: Carboplatin + Pemetrexed (CP)

Serious events: 49 serious events

Other events: 222 other events

Deaths: 65 deaths

Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP)

Serious events: 42 serious events

Other events: 129 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Executive Medical Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Study site and investigator shall not publish study results except as required by law or as specified in a separate, written agreement between the sponsor and the study site or the investigator.
Publication restrictions are in place

Restriction type: OTHER