Description:
The purpose of this study is to assess the efficacy of lazertinib, amivantamab, carboplatin,
and pemetrexed (LACP) compared with carboplatin and pemetrexed (CP), in participants with
locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21
L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure.
Title
- Brief Title: 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
- Official Title: A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure
Clinical Trial IDs
- ORG STUDY ID:
CR109061
- SECONDARY ID:
2021-001825-33
- SECONDARY ID:
61186372NSC3002
- NCT ID:
NCT04988295
Conditions
- Carcinoma, Non-Small-Cell Lung
Interventions
Drug | Synonyms | Arms |
---|
Lazertinib | JNJ-73841937, YH-25448 | Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed) |
Amivantamab | JNJ-61186372 | Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed) |
Pemetrexed | | Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed) |
Carboplatin | | Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed) |
Purpose
The purpose of this study is to assess the efficacy of lazertinib, amivantamab, carboplatin,
and pemetrexed (LACP) compared with carboplatin and pemetrexed (CP), in participants with
locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21
L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure.
Detailed Description
Lung cancer is one of the most common types of cancer and is the most common cause of death
from cancer. NSCLC accounts for approximately 85 percent (%) of lung cancers. Advanced NSCLC
is a serious terminal illness that accounts for approximately 20% of all cancer mortality,
and until recently had a median overall survival (OS) of approximately 1 year. Amivantamab
(JNJ-61186372) is a low fucose, fully human immunoglobulin (IgG)1-based bispecific antibody
directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine kinase receptors.
It shows clinical activity against tumors with primary activating EGFR mutations Exon 19del
and Exon 21 L858R substitution. Lazertinib (JNJ-73841937; YH-25448) is an oral, highly
potent, third-generation EGFR tyrosine kinase inhibitor (TKI). It selectively inhibits both
primary activating EGFR mutations (Exon 19del, Exon 21 L858R substitution) and the EGFR T790M
resistance mutation, with less inhibition of wild-type EGFR. The study consists of a
Screening Phase (up to 28 days), a Treatment Phase (from randomization until the End of
Treatment visit) and a Follow-up Phase (from End of Treatment Visit until the end of study,
death, lost to follow-up, or withdrawal of consent, whichever comes first). Safety will be
assessed by physical examinations, laboratory tests, vital signs, electrocardiograms, Eastern
Cooperative Oncology Group (ECOG) performance status, and monitoring of adverse events (AEs).
The total duration of the study is up to 48 months.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed) | Experimental | Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as intravenous (IV) infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Lazertinib, Pemetrexed, and Amivantamab as maintenance until disease progression. | - Lazertinib
- Amivantamab
- Pemetrexed
- Carboplatin
|
Arm B: CP (Carboplatin and Pemetrexed) | Active Comparator | Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression. | |
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed) | Experimental | Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression. | - Amivantamab
- Pemetrexed
- Carboplatin
|
Eligibility Criteria
Inclusion Criteria:
- Participant must have at least 1 measurable lesion, according to Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
- Participant must have histologically or cytologically confirmed, locally advanced or
metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after
the tine of locally advanced metastatic disease diagnosis by either epidermal growth
factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
- A participant with definitively, locally treated brain metastases must be clinically
stable and asymptomatic, with or without low-dose corticosteroid treatment (less than
or equal to [<=]10 milligrams [mg]) prednisone or equivalent), for at least 14 days
prior to randomization
- Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Any toxicities from prior systemic anticancer therapy must have resolved to National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version
5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral
neuropathy, or Grade less than [<] 2 hypothyroidism stable on hormone replacement)
- A woman of childbearing potential must have a negative serum pregnancy 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
- Participant must have progressed on or after osimertinib monotherapy as the most
recent line of treatment. Osimertinib must have been administered as either the
first-line treatment for locally advanced or metastatic disease or in the second- line
setting after prior treatment with first- or second-generation EGFR tyrosine kinase
inhibitor (TKI). Participants who received either neoadjuvant and/or adjuvant
treatment are eligible if progression to locally advanced or metastatic disease
occurred at least 12 months after the last dose of such therapy and then the
participant progressed on or after osimertinib in the locally advanced or metastatic
setting. Treatment with osimertinib must be discontinued at least 8 days (4
half-lives) prior to randomization (that is last dose no later than Day -8)
Exclusion Criteria:
- Participant received radiotherapy for palliative treatment of NSCLC less than 14 days
prior to randomization
- Participant has active brain metastases not definitively treated with local therapy
- Participant has leptomeningeal disease, or participant has spinal cord compression not
definitively treated with surgery or radiation
- Participant has known small cell transformation
- Participant has a medical history of interstitial lung disease (ILD), including
drug-induced ILD or radiation pneumonitis
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Secondary Outcome Measures
Measure: | Objective Response as Assessed by BICR |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria. |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 48 months |
Safety Issue: | |
Description: | Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause. |
Measure: | Duration of Response (DoR) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR. |
Measure: | Time to Subsequent Therapy (TTST) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first. |
Measure: | Progression-Free Survival After First Subsequent Therapy (PFS2) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first. |
Measure: | Time to Symptomatic Progression (TTSP) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms. |
Measure: | Intracranial PFS |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1. |
Measure: | Number of Participants with Adverse Events (AEs) |
Time Frame: | Up to 48 months |
Safety Issue: | |
Description: | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Measure: | Number of Participants with Clinical Laboratory Abnormalities |
Time Frame: | Up to 48 months |
Safety Issue: | |
Description: | Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported. |
Measure: | Serum Concentration of Amivantamab |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | Serum samples will be analyzed to determine concentrations of amivantamab. |
Measure: | Plasma Concentration of Lazertinib |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | Plasma samples will be analyzed to determine concentrations of lazertinib. |
Measure: | Number of Participants with Anti-Amivantamab Antibodies |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | Number of participants with anti-amivantamab antibodies will be reported. |
Measure: | Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology. |
Measure: | European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. |
Measure: | Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 3, 2021