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 (PAPILLON)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Pemetrexed; Drug: Amivantamab; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04538664

2020-000633-40 (EudraCT Number)

2023-506033-29-00 (Registry Identifier)

61186372NSC3001 (Other Identifier)

CR108850

Details and patient eligibility

About

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.

Enrollment: 308 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

308 participants in 2 patient groups

Arm A: Amivantamab + Chemotherapy

Experimental group

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.

Treatment:

Drug: Carboplatin

Drug: Pemetrexed

Drug: Amivantamab

Drug: Pemetrexed

Arm B: Chemotherapy Alone

Experimental group

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.

Treatment:

Drug: Carboplatin

Drug: Pemetrexed

Drug: Pemetrexed