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 study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of JNJ-61186372 as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (JNJ-61186372 in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for 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:JNJ-61186372 Monotherapy+Combination Dose Escalations
JNJ-61186372Part 2:JNJ-61186372 Monotherapy+Combination Dose Expansion
LazertinibPart 1:JNJ-61186372 Monotherapy+Combination Dose Escalations
CarboplatinPart 1:JNJ-61186372 Monotherapy+Combination Dose Escalations
PemetrexedPart 1:JNJ-61186372 Monotherapy+Combination Dose Escalations

Purpose

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of JNJ-61186372 as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (JNJ-61186372 in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for 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 JNJ-61186372
      Monotherapy and Combination Dose Escalations and Part 2 JNJ-61186372 Monotherapy and
      Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be enrolled
      into cohorts at increasing dose levels of JNJ-61186372 monotherapy, the RP2CD of the
      JNJ-61186372 and lazertinib combination which will be administered in 28 day treatment
      cycles, and RP2q3W of JNJ-61186372 in combination with standard of care carboplatin and
      pemetrexed (chemotherapy combination) which will be administered in 21 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 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 as a monotherapy at the RP2D
      regimen(s), or in combination with lazertinib at the RP2CD regimen. For both parts, the study
      consists of following periods: an optional pre-Screening period; 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(+7) days after the last dose of study drug or prior to starting any subsequent
      anti-cancer treatment, whichever comes first); 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:JNJ-61186372 Monotherapy+Combination Dose EscalationsExperimentalThe first cohort of participants will receive intravenous (IV) infusions of JNJ-61186372 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of JNJ-61186372 at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of JNJ-61186372 once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and JNJ-61186372 on Cycle 1 Day 1 (C1D1) prior to initiation of JNJ-61186372 (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day JNJ-61186372 treatment cycle. In Chemotherapy Combination Cohort, participants will receive JNJ-61186372, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.
  • JNJ-61186372
  • Lazertinib
  • Carboplatin
  • Pemetrexed
Part 2:JNJ-61186372 Monotherapy+Combination Dose ExpansionExperimentalParticipants will receive IV infusion of JNJ-61186372 as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.
  • JNJ-61186372
  • Lazertinib

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 prior standard of care therapy (Cohort C and hepatocyte growth factor
             receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine kinase
             inhibitor [TKI]; Cohort D and MET-2: platinum-based chemotherapy) for metastatic
             disease, or be ineligible for, or have refused all other currently available
             therapeutic options. In cases where participants refuse currently available
             therapeutic options, this must be documented in the study records. For Part 1
             Chemotherapy Combination Cohort only: Participants must have histologically or
             cytologically confirmed NSCLC that is metastatic or unresectable and be eligible for
             treatment with combination carboplatin and pemetrexed, in accordance with standard of
             care, and be willing to receive additional investigational therapy with JNJ-61186372

          -  For Part 1 Combination Dose Escalation with lazertinib only: Participants must have
             been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment
             naïve for metastatic disease, without access to third generation TKI in the front-line
             setting, or (b) have progressed after front-line treatment with first (erlotinib or
             gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or
             (c) have been treated with a third generation TKI (eg, osimertinib) in either the
             front line or second-line setting, and are not eligible for enrollment in either
             Cohort C or MET-1. For Part 1 Chemotherapy Combination Cohort: Participants may be
             diagnosed with EGFR mutated or EGFR wild type NSCLC. 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, E, and MET-1), as well as marketed TKI-resistant
             mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14
             skipping mutation (Cohort MET-2). Documentation of primary activating EGFR or cMet
             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: Cohorts A and B: Participants EGFR mutated 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 with primary EGFR
             mutated disease, with a documented EGFR alteration (example, C797S) mediating
             resistance to previous treatment with a third generation EGFR TKI (for example,
             osimertinib), in participants with primary Exon 20ins disease, the documented EGFR
             alteration may arise following 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 and have not been previously
             treated with a TKI with known activity against Exon 20ins disease (exampe,
             poziotinib). Cohort MET-1: Participants with documented primary EGFR mutated disease
             and documented MET amplification or MET mutation after progression on any EGFR TKI.
             Participants with disease characterized by both MET amplification and EGFR resistance
             mutations to prior third generation EGFR TKI will be preferentially enrolled into
             Cohort C. Participants may have received or have been intolerant to prior
             platinum-based chemotherapy. Cohort MET-2: Participants with documented primary MET
             Exon 14 skipping mutation non-small cell lung cancer (NSCLC). Cohort E (combination
             JNJ-61186372 and lazertinib): Participants must have been diagnosed with EGFR Exon
             19del or L858R activating mutation, and have progressed after first or second-line
             treatment with a third generation TKI (eg, osimertinib)

          -  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, or diabetes, ongoing or active infection, (that is,
             has discontinued all antibiotics for at least one week prior to first dose of study
             drug), or psychiatric illness/social situation that would limit compliance with study
             requirements. Participants with medical conditions requiring chronic continuous oxygen
             therapy are excluded. For Part 1 Chemotherapy Combination Cohort only: additionally,
             participants with active bleeding diathesis

          -  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 study drug. For agents with
             long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from
             previous anti-cancer 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 1 Combination Dose Escalation: Any previous treatment with
             systemic anti cancer immunotherapy, including but not limited to anti-PD-1,
             anti-PD-L1, and anti-CTLA-4 agents. For Part 1 Chemotherapy Combination Cohort only:
             Any previous treatment with systemic anti cancer immunotherapy in the past 3 months or
             localized radiotherapy to lung within the past 6 months. 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 TKI (example, Exon 20
             insertions). Cohort C and MET-1: 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). Cohort E (combination JNJ-61186372 and lazertinib): Any previous
             treatment in the metastatic setting with other than a first, second, or third
             generation EGFR TKI

          -  Participants with untreated brain metastases. Participants with definitively,
             locally-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.
             Exception: participants with asymptomatic, untreated brain metastases, each less than
             1 cm in diameter, may be eligible for JNJ 61186372 and lazertinib combination therapy
             in the Part 1 Combination Dose Escalation or Part 2 Combination Expansion Cohort E

          -  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) (each cycle is of 28 days)
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:Maximum Serum Concentration (Cmax) of Lzertinib
Time Frame:Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)
Safety Issue:
Description:Cmax is the maximum observed serum concentration of lazertinib.
Measure:Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib
Time Frame:Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)
Safety Issue:
Description:Tmax is defined as time to reach maximum observed serum concentration of lazertinib.
Measure:Trough Serum Concentration (Ctrough) of Lazertinib
Time Frame:Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)
Safety Issue:
Description: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 [+7] 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 [+7] 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 [+7] 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

Last Updated

May 29, 2020