Summary

for people ages 18 years and up (full criteria)
at UCLA UCSD
study started
estimated completion

Description

Summary

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) and recommended Phase 2 combination dose (RP2CD) (combination therapy) in participants with advanced non-small cell lung cancer (NSCLC).

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

Details

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, and the RP2CD of the JNJ-61186372 and lazertinib combination, 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 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 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.

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 Lung Neoplasms Carcinoma, Non-Small-Cell Lung Antibodies Immunoglobulins Antibodies, Bispecific Lazertinib

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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. In cases where participants refuse currently available therapeutic options, this must be documented in the study records
  • For Part 1 Combination Dose Escalation only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (b) 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 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 tyrosine kinase inhibitor [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 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. 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, who 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

You CAN'T join if...

  • 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 JNJ-61186372), or psychiatric illness/social situation that would limit compliance with study requirements. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded
  • 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 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 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) (example, Exon 20 insertions). Cohort C, MET-1, and MET-2: 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 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

Locations

  • UC San Diego Moores Cancer Center not yet accepting patients
    La Jolla California 92093 United States
  • David Geffen School of Medicine at UCLA not yet accepting patients
    Los Angeles California 90095 United States
  • Samuel Oschin Comprehensive Cancer Center Cedars-Sinai Medical Center accepting new patients
    West Hollywood California 90048 United States
  • Chao Family Comprehensive Cancer Center accepting new patients
    Orange California 92868 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Janssen Research & Development, LLC
Links
To learn how to participate in this trial please click here.
ID
NCT02609776
Phase
Phase 1
Study Type
Interventional
Last Updated