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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

NCT04988295

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04988295

Trial Eligibility

Document

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

DrugSynonymsArms
LazertinibJNJ-73841937, YH-25448Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed)
AmivantamabJNJ-61186372Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed)
PemetrexedArm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed)
CarboplatinArm 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

NameTypeDescriptionInterventions
Arm A: LACP (Lazertinib, Amivantamab, Carboplatin, and Pemetrexed)ExperimentalParticipants 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 ComparatorParticipants 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.
  • Pemetrexed
  • Carboplatin
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)ExperimentalParticipants 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