A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 in Adult Participants With Advanced or Refractory Solid Tumors or Lymphoma

This is a first-in-human, non-randomized (individuals will not be assigned by chance to study
treatments), open-label (individuals will know the identity of study treatments), multicenter
(more than 1 hospital work on a study), Phase 1 study. The study consists of 4 parts. Part 1
is the dose-escalation phase, which will be guided by pharmacokinetics, pharmacodynamics and
safety. In part 1, safe and biologically active Phase 2 doses (recommended Phase 2 doses
[RP2D]) for JNJ-42756493 will be primarily assessed. Participants will be enrolled in
sequential cohorts (first cohort will receive the starting dose and subsequent cohorts will
receive increased doses of JNJ-42756493). Part 2 is the Dose Confirmation Phase, which
consists of a pre and post treatment tumor biopsy cohorts to confirm the RP2D based on the
pharmacodynamic effect of JNJ-42756493 on fibroblast growth factor receptor (FGFR) signaling
pathway in tumor. Part 3 is the first Dose Expansion Phase, which is designed to evaluate
inclusion biomarkers and preliminary clinical activity at the first RP2D. It consists of 4
expansion cohorts, 1 each for squamous cell lung cancer, small cell lung cancer, breast
cancer, other solid tumors (Cohorts A, B, C, and D). Part 4 is the second Dose Expansion
Phase, which is designed to evaluate inclusion biomarkers and preliminary clinical activity
at the second RP2D. Biomarker eligibility has also been refined based on emerging data. It
consists of 2 expansion cohorts, Cohort E for non-small cell lung cancer and Cohort F for
select solid tumors including breast, urothelial, GBM, ovarian, head & neck, esophageal,
gastric, and cholangiocarcinoma (Cohorts E and F). Enrollment of some cohorts may be
discontinued due to lack of enrollment or for futility. The study is estimated to take
approximately 48 months to complete. Participants' safety will be monitored throughout the
study.

Inclusion Criteria:

- Histologically or cytologically confirmed: solid malignancy or lymphoma that is
metastatic or unresectable, and for which standard curative treatment is no longer
effective (Part 1); any type of advanced or refractory solid malignancy (excluding
lymphoma) that is metastatic or unresectable and for which standard curative treatment
is no longer effective (Part 2); advanced or refractory squamous non-small cell lung
cancer (Cohort A, Part 3), advanced or refractory small cell lung cancer (Cohort B,
Part 3), advanced or refractory breast cancer (Cohort C, Part 3), any type of advanced
or refractory solid malignancy (excluding lymphoma) ([consisting of one of the
following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma
multiforme (GBM), ovarian or prostate]) (Cohort D, Part 3), advanced or refractory non
small cell lung cancer(Cohort E, Part 4), any type of advanced or refractory solid
malignancy (consisting of one of the following: Breast, Urothelial, GBM, Ovarian, Head
& Neck, Esophageal, Gastric, and Cholangiocarcinoma) (Cohort F, Part 4)

- Eastern Cooperative Oncology Group performance status score 0 or 1

- Adequate bone marrow, liver, and renal function within the 14 days prior to Day 1 of
Cycle 1 of study drug up until pre-dose of Cycle 1

- Magnesium within 0.85 to 1.25 * institutional normal limits, Sodium greater than or
equal to 130 milli equivalent per liter, Potassium within institutional normal limits
(within 14 days prior to Day 1 of Cycle 1 up until pre-dose of Cycle 1)

Exclusion Criteria:

- Chemotherapy, targeted therapies, radiotherapy, immunotherapy, or treatment with an
investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug,
whichever is longer and up to a maximum of 4 weeks (in the case of nitrosoureas and
mitomycin C within 6 weeks) before the first administration of study drug. Localized
radiation therapy and ongoing luteinizing hormone-releasing hormone (LHRH) agonists,
bisphosphonates and denosumab, are permitted

- Participants with GBM can be enrolled 2 weeks after last treatment

- History or current condition of uncontrolled cardiovascular disease

- Participants with persistent phosphate greater than upper limit of normal during
screening (within 14 days prior to Day 1 of Cycle 1 up until pre-dose of Cycle 1) and
despite medical management of phosphate levels

- Participants taking medications known to have a significant risk of causing QTc
prolongation and Torsades de Pointes

- Left ventricular ejection fraction (LVEF) less than 50 percent as assessed by
echocardiography (or multi-gated acquisition) performed at screening

- Any medical condition that requires intact wound healing capacity and is expected to
endanger participant safety if wound healing capacity would be severely reduced during
administration of the investigational agent

- Participants not recovered from reversible toxicity of prior anticancer therapy
(except toxicities which are not clinically significant such as alopecia, skin
discoloration, or Grade 1 neuropathy)