Phase 1 study of the combination of rogaratinib with copanlisib in patients with FGFR-positive, locally advanced or metastatic solid tumors.
Dose escalation part: locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.
Dose expansion part: locally advanced or metastatic urothelial carcinoma that is mRNA-positive for at least one FGFR1-4 subtype.
The primary objective of this study is to determine the safety, tolerability, and maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of rogaratinib in combination with copanlisib in patients with FGFR mRNApositive, locally advanced or metastatic solid tumors.
In- and exclusion Criteria
Inclusion criteria applicable to 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.
Inclusion criteria applicable to 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, meeting all of the following criteria:
• Histologically confirmed
• Patients with mixed histology are required to have a dominant
transitional cell pattern.
• Locally advanced (T4, any N; or any T, N2-3) or metastatic disease
(any T, any N, and M1).
• Locally advanced bladder cancer must be unresectable i.e. invading the
pelvic or abdominal wall (stage T4b) or presenting with bulky nodal
Previous or concurrent cancer that is distinct from tumor for which the patient is enrolled in study, except
• curatively treated cervical carcinoma in situ
• treated basal-cell carcinoma
• localized prostate cancer treated with curative intent and known absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL undergoing active surveillance and treatment-naïve)
• any cancer curatively treated > 3 years before planned start of study treatment.
• Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or 6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies)
• Previous radiotherapy is acceptable under the following conditions: Therapy completed more than 4 weeks before the baseline (at screening) scan, Patients must have recovered from all therapy-related toxicities, If the site of previous radiotherapy is the only site of disease, it should show evidence of disease progression.
• Prior local intra-vesical chemotherapy or prior local immunotherapy (e.g. with Bacillus Calmette-Guérin [BCG]) is allowed if completed at least 4 weeks before the first study treatment administration.
• Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation
This study is a Phase 1 open label, non-randomized, single arm, multicenter, 2-part dose escalation and dose expansion study of rogaratinib in combination with copanlisib in patients with FGFR mRNA-positive, locally advanced or metastatic solid tumors.
Bayer AG, D-51368 Leverkusen, Germany
University Hospital of Cologne
Dep. I of Internal Medicine
Phone: +49 221 478 87008
Fax: +49 221 478 87010
PD Dr. Lucia Nogova, MSc,
Last Update: 1. February 2019