TriangleNCT04538664 · CITED IN SOURCE DOCUMENTS
A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-08-31
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
Objective Response Rate (ORR)
Duration of Response (DoR)
Overall Survival (OS)
Time to Subsequent Therapy (TST)
Progression-Free Survival After First Subsequent Therapy (PFS2)
Time to Symptomatic Progression (TTSP)
Number of Participants Treatment-emergent Adverse Events (TEAEs)
Number of Participants TEAEs With Severity
Number of Participants With Clinical Laboratory Abnormalities
Number of Participants With Vital Signs Abnormalities
Number of Participants With Physical Examination Abnormalities
Serum Concentration of Amivantamab
Number of Participants With Anti-Amivantamab Antibodies
Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion 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. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
- intervention Names
- Drug: Amivantamab
- Drug: Pemetrexed
- Drug: Carboplatin
- label
- Arm A: Amivantamab + Chemotherapy
- type
- EXPERIMENTAL
- description
- Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
- intervention Names
- Drug: Carboplatin
- Drug: Pemetrexed
- label
- Arm B: Chemotherapy Alone
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm A: Amivantamab + Chemotherapy
- description
- 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.
- name
- Amivantamab
- other Names
- JNJ-61186372
- type
- DRUG
- arm Group Labels
- Arm A: Amivantamab + Chemotherapy
- description
- 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.
- name
- Pemetrexed
- type
- DRUG
- arm Group Labels
- Arm A: Amivantamab + Chemotherapy
- Arm B: Chemotherapy Alone
- description
- Carboplatin will be administered as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.
- name
- Carboplatin
- type
- DRUG
- arm Group Labels
- Arm B: Chemotherapy Alone
- description
- 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 B and will continue the same treatment in OLE phase then in LTE phase.
- name
- Pemetrexed
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 308
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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).
- measure
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
- time Frame
- From randomization to either disease progression or death whichever occurs first (up to 29 months)
- secondary Outcomes
- measure
- Objective Response Rate (ORR)
- time Frame
- Up to 5 years 3 months
- measure
- Duration of Response (DoR)
- time Frame
- Up to 5 years 3 months
- measure
- Overall Survival (OS)
- time Frame
- Up to 5 years 3 months
- measure
- Time to Subsequent Therapy (TST)
- time Frame
- Up to 5 years 3 months
- measure
- Progression-Free Survival After First Subsequent Therapy (PFS2)
- time Frame
- Up to 5 years 3 months
- measure
- Time to Symptomatic Progression (TTSP)
- time Frame
- Up to 5 years 3 months
- measure
- Number of Participants Treatment-emergent Adverse Events (TEAEs)
- time Frame
- From Day 1 to 5 years 2 months
- measure
- Number of Participants TEAEs With Severity
- time Frame
- From Day 1 to 5 years 2 months
- measure
- Number of Participants With Clinical Laboratory Abnormalities
- time Frame
- Up to 5 years 3 months
- measure
- Number of Participants With Vital Signs Abnormalities
- time Frame
- Up to 5 years 3 months
- measure
- Number of Participants With Physical Examination Abnormalities
- time Frame
- Up to 5 years 3 months
- measure
- Serum Concentration of Amivantamab
- time Frame
- Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Full study description
- 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.
Source references
- references
- citation
- Tang K, Wu F, Yang F, Yao Y, Zhao Y, Zhou J, Sun P, Wang D, Lv D, Wang H, Hu Y, Li Q, Song Y, Gao G, Pan F, Bhattacharya A, Baig M, Lorenzini PA, Wortman-Vayn H, Agrawal T, Zhou C. Amivantamab plus chemotherapy vs. chemotherapy as first-line treatment in Chinese mainland patients with EGFR exon 20 insertion non-small cell lung cancer: Subgroup analysis of the randomized PAPILLON trial. Chin Med J (Engl). 2026 May 26. doi: 10.1097/CM9.0000000000004134. Online ahead of print.
- pmid
- 42192224
- type
- DERIVED
- citation
- Zhou C, Tang KJ, Liu B, Kim SW, Kitazono S, Ono A, Thiagarajan M, Hung JY, Boyer M, CIl T, Yao Y, Nagarkar R, Xie J, Bhattacharya A, Wortman-Vayn H, Baig M, Agrawal T, Lorenzini P, Lee SH, Cho BC. Amivantamab plus chemotherapy versus chemotherapy for first-line treatment of participants with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer: PAPILLON Asia subgroup analysis. Lung Cancer. 2026 Mar;213:109302. doi: 10.1016/j.lungcan.2026.109302. Epub 2026 Feb 2.
- pmid
- 41671628
- type
- DERIVED
- citation
- Sanborn RE, Zhou C, Tang KJ, Cho BC, Cheng S, Popat S, Ono A, Lu S, Majem M, Aguilar A, Del Rosario Garcia Campelo M, Hayashi H, Lee KY, Lee SH, Delmonte A, Alatorre-Alexander J, Richardson G, Santos V, Dooms C, Sabari JK, Shu CA, Girard N, Mansfield AS, Park K, Xia Y, Bhattacharya A, Buyukkaramikli N, Perualila N, Diels J, Acharya S, Chandler C, Proskorovsky I, Dearden L, Wortman-Vayn H, Mahadevia PJ, Knoblauch RE, Agrawal T, Baig M, Felip E. Amivantamab-Chemotherapy in Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions: Impact of Treatment Crossover and Other Endpoints from the Phase III PAPILLON Study. Target Oncol. 2025 Nov;20(6):979-989. doi: 10.1007/s11523-025-01182-0. Epub 2025 Nov 3.
- pmid
- 41184595
- type
- DERIVED
- citation
- Kitazono S, Ono A, Kawamura T, Hataji O, Tanaka H, Matsumoto S, Watanabe N, Nagashima H, Oki M, Takahashi M, Anazawa T, Shirai T, Yamashita A, Wortman-Vayn H, Bhattacharya A, Agrawal T, Baig M, Knoblauch RE, Hayashi H. Amivantamab Plus Chemotherapy in Japanese Patients With EGFR Exon 20 Insertions NSCLC. Cancer Sci. 2025 Nov;116(11):3139-3148. doi: 10.1111/cas.70180. Epub 2025 Sep 8.
- pmid
- 40922529
- type
- DERIVED
- citation
- Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourao Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med. 2023 Nov 30;389(22):2039-2051. doi: 10.1056/NEJMoa2306441. Epub 2023 Oct 21.
- pmid
- 37870976
- type
- DERIVED
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Preserved source evidence · Not medical advice