Clinical Trials /

Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

NCT02609776

Description:

The purpose of this study is to evaluate the safety and pharmacokinetics, establish a recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: CR108064
  • SECONDARY ID: 61186372EDI1001
  • SECONDARY ID: 2018-003908-38
  • NCT ID: NCT02609776

Conditions

  • Non-Small-Cell Lung Cancer

Interventions

DrugSynonymsArms
JNJ-61186372Part 1: Dose Escalation
JNJ-61186372Part 2: Dose Expansion

Purpose

The purpose of this study is to evaluate the safety and pharmacokinetics, establish a recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).

Detailed Description

      This open label (all participants know the identity of the study drug), multicenter (more
      than one study site), first-in-human study consists of 2 parts. Part 1 is a dose escalation
      and Part 2 is a dose expansion cohort. In Part 1, participants with evaluable non-small cell
      lung cancer (NSCLC) will be enrolled into cohorts at increasing dose levels of JNJ-61186372,
      which will be administered in 28 day treatment cycles. The dose will be escalated until the
      maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is
      reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will
      complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then
      escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to
      determine one or more recommended phase 2 dose (RP2D) regimen(s). In Part 2, participants
      with documented epidermal growth factor receptor (EGFR) mutations and measurable disease,
      whose disease has progressed after previous treatment will be enrolled and receive
      JNJ-61186372 at the RP2D determined in Part 1. For both parts, the study consists of 3
      periods: a Screening period (up to 28 days prior to the first dose of study drug); a
      Treatment period (first dose of study drug until 30 days after the last dose of study drug);
      and a Follow Up period (approximately 6 months). All participants will be followed for
      survival in the post-treatment follow-up period until the end of study and safety will be
      monitored throughout the study.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalThe first cohort of participants will receive intravenous infusions of JNJ-61186372 at a dose of 140 milligram (mg). Each subsequent cohort will receive intravenous infusions of JNJ-61186372 at an increased dose level. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. Participants will receive intravenous infusion of JNJ-61186372 once weekly during cycle 1 and once every 2 weeks during subsequent cycles. The duration of each treatment cycle is 28 days.
  • JNJ-61186372
Part 2: Dose ExpansionExperimentalParticipants will receive intravenous infusion of JNJ-61186372 at the recommended Phase 2 dose (RP2D) regimen(s) once weekly during cycle 1 and once in 2 weeks for subsequent cycles. The duration of each treatment cycle is 28 days.
  • JNJ-61186372

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must have histologically or cytologically confirmed non-small cell lung
             cancer (NSCLC) that is metastatic or unresectable. Participants must have either
             progressed after receiving prior therapy for metastatic disease, or be ineligible for,
             or have refused all other currently available therapeutic options

          -  For Part 2 only: Participants must also have disease with a previously diagnosed
             activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor
             sensitive primary mutations such as Exon 19 deletion and L858R [Cohort C], as well as
             marketed tyrosine kinase inhibitor [TKI] -resistant mutations such as Exon 20
             insertion [Cohort C and D]). Documentation of EGFR mutation eligibility by
             CLIA-certified laboratory (or equivalent) testing is required

          -  For Part 1: Participant must have evaluable disease. For Part 2: Participant must have
             measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1

          -  For Part 2: Cohort A and B: Participants disease must have most recently progressed
             following treatment with a marketed EGFR inhibitor. Exception: In participants
             diagnosed with mutations associated with de novo EGFR inhibitor resistance (for
             example, exon 20 insertions), only previous treatment with combination platinum-based
             chemotherapy is required. Cohort C: Participants must have documented EGFR or
             mesenchymal-epithelial transition (cMET) alterations mediating resistance to previous
             treatment with a third generation TKI (for example, osimertinib), or in the case of
             primary Exon 20ins disease, previous treatment with a TKI with known activity against
             Exon 20ins disease (for example, poziotinib). Cohort D: Participants must have been
             previously diagnosed with an EGFR Exon 20 insertion

          -  Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0
             or 1

        Exclusion Criteria:

          -  Participant has uncontrolled inter-current illness, including but not limited to
             poorly controlled hypertension, other cardiovascular disease, or diabetes, ongoing or
             active infection, or psychiatric illness/social situation that would limit compliance
             with study requirements

          -  Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or
             treatment with an investigational anticancer agent within 2 weeks or 4 half-lives
             whichever is longer, before the first administration of JNJ-61186372. For agents with
             long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from
             previous anticancer therapies should have resolved to baseline levels or to Grade 1 or
             less, (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral
             neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement).
             For Part 2 only: Cohorts A and B: Prior treatment with chemotherapy for metastatic
             disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR
             tyrosine kinase inhibitor (TKI) (eg, exon 20 insertions). Cohort C: Prior treatment
             with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance
             therapy is not included). Cohort D: Previous treatment with an EGFR TKI with activity
             against EGFR Exon 20 insertions (such as poziotinib)

          -  Participants with untreated brain metastases. Participants with treated metastases
             that are clinically stable and asymptomatic for at least 2 weeks and who are off or
             receiving low-dose corticosteroid treatment (<=10 mg prednisone or equivalent) for at
             least 2 weeks prior to study treatment are eligible

          -  Participant has a history of malignancy other than the disease under study within 3
             years before Screening (exceptions are squamous and basal cell carcinomas of the skin
             and carcinoma in situ of the cervix, or malignancy that in the opinion of the
             investigator, with concurrence with the sponsor's medical monitor, is considered cured
             with or minimal risk of recurrence within a year from screening)

          -  Participant has not fully recovered from major surgery or significant traumatic injury
             prior the first dose of study drug or expects to have major surgery during the study
             period or within 6 months after the last dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame:Up to Day 28
Safety Issue:
Description:The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

Secondary Outcome Measures

Measure:Maximum Serum Concentration (Cmax) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months)
Safety Issue:
Description:The Cmax is the maximum observed serum concentration of JNJ-61186372.
Measure:Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:The Tmax is defined as time to reach maximum observed serum concentration of JNJ-61186372.
Measure:Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:The AUC(t1-t2) is the area under the serum JNJ-61186372 concentration-time curve from time t1 to t2.
Measure:Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)
Measure:Trough Serum Concentration (Ctrough) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:The Ctrough is the observed serum concentration immediately prior to the next administration.
Measure:Accumulation ratio (R) of JNJ-61186372
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.
Measure:Number of Participants With Anti-Drug Antibodies (ADA)
Time Frame:Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)
Safety Issue:
Description:Serum levels of antibodies to JNJ-61186372 for evaluation of potential immunogenicity.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to End of Treatment Follow Up Period (30 days after the last dose)
Safety Issue:
Description:PFS is defined as the time from first infusion of study drug to PD or death due to any cause.
Measure:Time to Treatment Failure (TTF)
Time Frame:Up to End of Treatment Follow Up Period (30 days after the last dose)
Safety Issue:
Description:TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.
Measure:Overall Survival (OS)
Time Frame:Up to End of Treatment Follow Up Period (30 days after the last dose)
Safety Issue:
Description:OS is defined as the time from first infusion of study drug to death due to any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Trial Keywords

  • Non-Small-Cell Lung Cancer
  • JNJ-61186372
  • First-in-Human
  • Human Bispecific Epidermal Growth Factor Receptor (EGFR)
  • c-Mesenchymal-Epithelial Transition (cMet) Antibody
  • JNJ372
  • Exon 20
  • Exon 20 insertion
  • Tyrosine Kinase Inhibitor (TKI) Resistant
  • TKI Resistance
  • EGFR C797s
  • Met Amplification
  • Met + EGFR bispecific

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