Description:
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.
Title
- Brief Title: 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
- Official Title: A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
CR108850
- SECONDARY ID:
2020-000633-40
- SECONDARY ID:
61186372NSC3001
- NCT ID:
NCT04538664
Conditions
- Carcinoma, Non-Small-Cell Lung
Interventions
| Drug | Synonyms | Arms |
|---|
| Amivantamab | JNJ-61186372 | Arm A: Amivantamab + Chemotherapy |
| Pemetrexed | | Arm A: Amivantamab + Chemotherapy |
| Carboplatin | | Arm A: Amivantamab + Chemotherapy |
Purpose
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.
Detailed Description
Lung cancer is one of the most common types of cancer and is the most common cause of death
from cancer (almost 20 percent [%] of cancer deaths); NSCLC accounts for 80% to 85% of lung
cancers. Amivantamab (JNJ-61186372) is a low fucose, fully human immunoglobulin G1
(IgG1)-based bispecific antibody directed against epidermal growth factor receptor (EGFR) and
mesenchymal-epithelial transition (MET) tyrosine kinase receptors that is being developed for
the treatment of solid tumors. The hypothesis is that amivantamab, when given in combination
with standard of care carboplatin-pemetrexed chemotherapy, will prolong PFS compared with
carboplatin-pemetrexed in patients with locally advanced or metastatic NSCLC characterized by
EGFR Exon 20ins activating mutations. The study will include a Screening phase (28 days), a
Treatment phase (from Cycle 1 Day 1 [21-day cycle] till end of treatment [30 days after last
dose]) and a Follow up phase (from the end of treatment visit and until the end of study,
death, loss to follow-up, or withdrawal of consent from participation in the study, whichever
comes first). An independent data monitoring committee (IDMC) will be commissioned for the
periodic review of safety and tolerability data, as well as planned efficacy analyses.
Efficacy assessments will include disease assessment, symptomatic progression and
patient-reported outcome. Safety assessments will include physical examinations, vital signs,
electrocardiograms (ECGs), Eastern Cooperative Oncology Group (ECOG) performance status and
clinical safety laboratory assessments (serum chemistry, hematology, coagulation, and
urinalysis). The total duration of the study is up to 48 months.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A: Amivantamab + Chemotherapy | Experimental | 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. | - Amivantamab
- Pemetrexed
- Carboplatin
|
| Arm B: Chemotherapy Alone | Experimental | 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. | |
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
| 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 as Assessed by Blinded Independent Central Review (BICR) |
| Time Frame: | Up to 18 months |
| Safety Issue: | |
| Description: | PFS is defined as the time from randomization until the date of objective disease progression based on blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death (by any cause) in the absence of progression, whichever comes first. |
Secondary Outcome Measures
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria. |
| Measure: | Duration of Response (DoR) |
| Time Frame: | Up to 48 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 as determined by the investigator 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: | Time to Subsequent Therapy (TST) |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | TST 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. |
| Measure: | Progression-Free Survival After First Subsequent Therapy (PFS2) |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | PFS2 is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS or death after starting the next line of treatment. |
| Measure: | Time to Symptomatic Progression (TTSP) |
| Time Frame: | Up to 48 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: | Incidence and Severity of 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 urine samples) will be reported. |
| Measure: | Number of Participants with Vital Signs Abnormalities |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported. |
| Measure: | Number of Participants with Physical Examination Abnormalities |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | Number of participants with physical examination abnormalities will be reported. |
| Measure: | Serum Concentration of Amivantamab |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | Serum samples will be analyzed to determine concentrations of amivantamab. |
| Measure: | Number of Participants with Anti-Amivantamab Antibodies |
| Time Frame: | Up to 48 months |
| Safety Issue: | |
| Description: | Number of participants with antibodies to amivantamab will be reported. |
| Measure: | European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) |
| Time Frame: | Up to 48 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 48 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: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Trial Keywords
- EGFR Exon20ins Mutation
- NSCLC
Last Updated
August 20, 2021
