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
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).
18 Years and up
Accepting Healthy Volunteers?
- 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 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 enrolled into Cohort C. Cohort MET-2: Participants with documented primary MET Exon 14 skipping mutation non-small cell lung cancer (NSCLC)
- Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- 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 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) (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)
- 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