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

Advanced or Metastatic Solid Tumor Clinical Trial

— ROCOCO  

Official title:

A Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the Combination of Rogaratinib and Copanlisib in Patients With FGFR-positive, Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03517956
• Other study ID #: 19774
• Secondary ID: 2018-000419-26
• Status: Completed
• Phase: Phase 1
• Start date: July 25, 2018
• Est. completion date: February 1, 2021

Study information

• Verified date: July 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) and efficacy of rogaratinib in combination with copanlisib in patients with locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

The secondary objectives of this study are to characterize the pharmacokinetics (PK) of rogaratinib and copanlisib alone and in combination, and to assess the anti-tumor efficacy of rogaratinib in combination with copanlisib for locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 m*2 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 the 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); 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).

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• Rogaratinib (BAY1163877)
Dose escalation: Starting dose is rogaratinib 400 mg twice daily (b.i.d.) in continuous 28-day cycles from Cycle 1 Day 3 onwards. Dose expansion: With dose identified in dose escalation part.
• Copanlisib (BAY80-6946)
Dose escalation: Starting dose is 45 mg on Days 1, 8 and 15 of each 28-day cycle. Dose expansion: With dose identified in dose escalation part.

Locations

Country	Name	City	State
Belgium	CU Saint-Luc/UZ St-Luc	Bruxelles - Brussel
Belgium	UZ Antwerpen	Edegem
Belgium	CHU de Liège	Liege
Germany	Krankenhaus Nordwest	Frankfurt	Hessen
Germany	Universitätsklinikum Köln	Köln	Nordrhein-Westfalen
Germany	Klinikum der Universität Würzburg	Würzburg
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Spain	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital Clínico Universitario de Valencia	Valencia
United States	University of Maryland	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Institute - Detroit	Detroit	Michigan
United States	USC Norris Hospital and Clinics	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Tyler Cancer Center	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Korea, Republic of,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)		Up to 32 months
Primary	Incidence of drug-related TEAEs		Up to 32 months
Primary	Incidence of treatment-emergent serious adverse events (TESAEs)		Up to 32 months
Primary	Incidence of Dose-limiting toxicities (DLTs)		Approximately 10 months
Primary	Objective response rate (ORR) at recommended dose	ORR in patients receiving the recommended dose of the rogaratinib-copanlisib-combination during the dose expansion part	Up to 32 months
Secondary	Maximum plasma concentration of Copanlisib (Cmax)		0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
Secondary	Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48))		0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
Secondary	Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8))		0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
Secondary	Maximum plasma concentration of Rogaratinib (Cmax)		0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
Secondary	Objective response rate (ORR)		Up to 32 months
Secondary	Disease control rate (DCR)		Up to 32 months
Secondary	Duration of response (DOR) for Partial Response and Complete Response		Up to 32 months
Secondary	Progression-free survival (PFS)		Up to 32 months
Secondary	Overall survival (OS)		Up to 32 months