This study is a first-in-human, open-label, multicenter, 3-part, Phase 1 study to evaluate the safety,
pharmacokinetics, pharmacodynamics, and clinical activity of JnJ-42756493 administered orally to
subjects [GreaterThanorequalTo]18 years of age with advanced or refractory solid malignancies or lymphoma who are not
candidates for approved or available therapies. each cycle will consist of 21 days of daily continuous
dosing or 28 days of intermittent dosing schedule.
For the rest of the cycles of Part 1 and any cycle of Part 2, the study drug will be administered once a day for 21 days without any drug-free period.
1. Be 18 years of age, or older.
2. Histologically or cytologically confirmed:
* In Part 1, any type of advanced or refractory solid malignancy or lymphoma that
is metastatic or unresectable, and for which standard curative treatment is no
* Any type of advanced or refractory solid malignancy (excluding lymphoma) that
is metastatic or unresectable.
* Subjects must meet the following molecular eligibility criteria (diagnosed at a
local or at a central laboratory): tumors that are KRAS wild type in combination
with any of the following: FGFR amplification with or without FGF ligand
co-amplification, FGFR activating mutations, FGFR translocations, or other
molecular aberrations leading to activation of the FGFR pathway).
* Subjects must be amenable to pre- and post-treatment biopsies.
* Cohort A: advanced or refractory squamous NSCLC and meets the molecular
eligibility criteria (diagnosed at a local or central laboratory) as defined in Part 2.
* Cohort B: advanced or refractory squamous SCLC and meets the molecular
eligibility criteria (diagnosed at a local or at a central laboratory) as defined in
* Cohort C: advanced or refractory breast cancer and meets the molecular
eligibility criteria (diagnosed at a local lab or central laboratory) as defined in
* Cohort D: any type of advanced or refractory solid malignancy (excluding
lymphoma) and meets the molecular eligibility criteria (diagnosed at a local lab or central laboratory) as defined in Part 2.
* For Part 3 Cohort A, B and D, no more than 3 lines of prior chemotherapies for
treating metastatic disease. For Part 3 Cohort C, there are no restrictions
regarding prior lines of chemotherapies.
3. For Part 3, the presence of measurable disease according to the Response Evaluation
Criteria in Solid Tumors (RECIST) Criteria, and documented disease progression as
defined by RECIST (Version 1.1) at baseline
4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
5.Adequate bone marrow, liver, and renal function within the 7 days prior to Day 1 of
Cycle 1 , as described below:
* Bone marrow function (without the support of cytokines and/or erythropoietin in
preceding 2 weeks):
Absolute neutrophil count (ANC) >1500/mm3
Platelet count >75,000/mm3
Hemoglobin >8.5 g/dL (without transfusion or demonstrate stability (i.e no
significant decline in Hb) for 2 weeks after transfusion)
* Liver function:
Total bilirubin <=1.5 x institutional upper limit of normal (ULN).
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <=2.5 x
institutional ULN in the absence of liver metastasis, or <=5.0 x institutional ULN
in the presence of liver metastasis.
* Renal function:
Serum creatinine <=institutional ULN or if serum creatinine is >institutional
ULN, the calculated creatinine clearance (Attachment 2) should be >=60
6. Serum electrolyte levels (magnesium, potassium) within 0.85 to 1.25x institutional
normal limits (within 7 days prior to Day 1 of Cycle 1).
7. Female subjects (if of child bearing potential) and male subjects (with a partner of
child bearing potential) must use medically acceptable methods of birth control before
study entry, for the duration of the study, and for at least 3 months after the last intake of
study drug. Male subjects must accept the use of condoms when sexually active during
the study. Medically acceptable methods of contraception that may be used by the
subject and/or his/her partner include oral contraceptives, contraceptive injections,
contraceptive patch, intrauterine device, double-barrier method, and surgical
sterilization (eg, confirmed successful vasectomy or tubal ligation).
8. Negative pregnancy test (urinary beta human chorionic gonadotropin [[BETA]-HCG]) at
Screening for women of child bearing potential who are sexually active.
9. Sign an informed consent document indicating that they understand the purpose of and
procedures required for the study and are willing to participate in the study.