Phase 1 Study of the Combination of Rogaratinib With Copanlisib in Patients With Fibroblast Growth Factor Receptor (FGFR)-Positive, Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

- High FGFR mRNA expression levels (RNAscope score of ≥3; measurement is part of this
protocol) in archival or fresh tumor biopsy specimen.

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

- At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors
(RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.

- Adequate bone marrow, liver and renal function.

- Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of
Diet in Renal Disease (MDRD) formula.

- Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal
(LLN) at the institution.

- Life expectancy of at least 3 months.

- For the dose escalation part: Patients with histologically confirmed, locally advanced
or metastatic solid tumors who are not candidates for or refuse standard therapy or
whose disease progressed and for which standard anti-cancer treatment is no longer
effective, excluding primary brain or spinal tumors. Patients who have been advised
with all standard treatment options and still refuse them must be documented and can
be allowed to enter the trial.

- For the dose expansion part: Patients with histologically confirmed, locally advanced
or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary
bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard
therapy or whose disease progressed and for which standard anticancer treatment is no
longer effective. Patients who have been advised with all standard treatment options
and still refuse them must be documented and can be allowed to enter the trial.

Exclusion Criteria:

- Previous or concurrent cancer that is distinct from tumor for which the patient is
enrolled in study, with exceptions

- Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or
6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies); with exceptions.

- Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to
treatment discontinuation (previous exposure is allowed in other circumstances). If
prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to
treatment discontinuation is different from the known safety profile of rogaratinib or
copanlisib, enrollment is allowed.

- Symptomatic brain or meningeal metastatic tumors unless the patient is >6 months from
definitive therapy, has no evidence of tumor growth on an imaging study and is
clinically stable with respect to the tumor at the start of study treatment. Also the
patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy
is acceptable provided that the dose is stable for one month prior to and following
screening radiographic studies).

- History or current condition of an uncontrolled cardiovascular disease including
congestive heart failure NYHA > Class 2, unstable angina (symptoms of angina at rest)
or new-onset angina (within last 3 months) or myocardial infarction within past 6
months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or
digoxin are permitted).

- Active hepatitis B (HBV) or C (HCV) infection.

- Active clinically serious infections (≥ CTCAE v4.03 Grade 2).