Eligibility Details:
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 Combination Dose Escalation 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 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
- 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 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 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
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
