Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Mitogens

Taxane

Rogaratinib treatment study arm, comprising

1. Pre-treatment period, including FGFR testing and screening,
2. Treatment period, and
3. Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".

Chemotherapy treatment study arm, comprising

1. Pre-treatment period, including FGFR testing and screening,
2. Treatment period, and
3. Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".

Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously

Rogaratinib (BAY1163877)

Chemotherapy as taxane (docetaxel or paclitaxel) or vinflunine administered through intravenous (i.v.) infusion every 3 weeks (on day 1 of a 21-day cycle) The choice of the chemotherapy is at the discretion of the investigator, taking into consideration the status of the authorization or treatment guidelines in the given country.

Chemotherapy

Bayer Study Director

This is a randomized, open-label, multicenter Phase 2/3 study to evaluate the efficacy and safety of rogaratinib (BAY 1163877) compared to chemotherapy in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy.

The primary objective is to demonstrate the superiority of rogaratinib over chemotherapy in terms of objective response rate (before: overall survivial) of urothelial carcinoma patients with FGFR positive tumors.

At randomization, patients will have locally advanced or metastatic urothelial carcinoma and have received at least one prior platinum-containing chemotherapy regimen. Only patients with FGFR1 or 3 positive tumors can be randomized into the study. Archival tumor tissue is adequate for testing of FGFR1 and 3 mRNA expressions, which will be determined centrally using an RNA in situ hybridization (RNA-ISH) test. Approximately 42 % of UC patients with locally advanced or metastatic UC are identified as FGFR-positive by the RNA-ISH cut-off applied.

Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma

A Randomized, Open Label, Multicenter Phase 2/3 Study to Evaluate the Efficacy and Safety of Rogaratinib (BAY1163877) Compared to Chemotherapy in Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma Who Have Received Prior Platinum-containing Chemotherapy

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR). participants for whom overall best response is not CR or PR, as well as participants without any post-baseline tumor assessment will be considered non-responders.

DCR was defined as the percentage of participants whose overall best response was not a progressive disease (i.e., CR, PR, stable disease \[SD\] or Non CR/Non PD).

Progression free survival (PFS) was defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment or both) or death due to any cause (if death occurred before progression was documented).

DOR (for patients with PR and CR only) was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression (including symptomatic deterioration) or death, whichever was earlier

A treatment-emergent event was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment

Bayer

A treatment-emergent adverse event reported in this study was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment.

Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.

Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).

Rogaratinib (BAY1163877)_Overall Population

Chemotherapy_Overall Population

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Cancer Category

Higher value/letter correlates to advanced stages of the malignancy. IIIA: The tumor has grown into the perivesical tissue or has spread to the prostate, uterus, or vagina, but has not spread to the lymph nodes or other organs, or cancer has spread to a single regional lymph node; IIIB: the tumor has spread to 2 or more regional lymph nodes or the common iliac lymph nodes; IVA: The cancer has spread to the pelvic wall or the abdominal wall but not to other parts of the body, or has spread to lymph nodes located outside of the pelvis; IVB: the tumor has spread to other parts of the body.

Cancer stage at study entry

PIK3CA: Phosphoinositide 3 kinase, catalytic subunit alpha isoform RAS: Rat sarcoma

PIK3CA and/or RAS activating mutations

FGFR expression from Targos

Therapeutic Area Head

Rogaratinib_WT Population

Chemotherapy_WT Population

Objective Response Rate (ORR) - Central Assessment

Disease-control Rate (DCR) - Central Assessment

Progression-free Survival (PFS) - Central Assessment

Duration of Response (DOR) - Central Assessment

Any TEAE

Any drug related TEAE

Number of Participants With Treatment Emergent Adverse Events

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Small Cell Lung Carcinoma

Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Adenoid Cystic

Small Cell Lung Cancer

Adenoid Cystic Carcinoma

Patients from completed Bayer clinical trials, who received rogaratinib as monotherapy or combination therapy for the treatment of cancer.

Participants will be treated with investigational drug following the treatment schedule and dosing instructions from the feeder-study protocol.

Any other drug specified in the protocol of the completed Bayer clinical trials that is used in combination with rogaratinib. Not all patients receive combination therapy.

Combination drug

The purpose of this study is to enable patients, who are currently receiving rogaratinib in a Bayer-sponsored clinical trial (incl. NCT01976741), to continue treatment after their respective study has been closed. Another aim is to learn if rogaratinib is safe and how it affects the body.

Rogaratinib is an investigational drug that may treat different types of cancer, incl. non-small-cell lung cancer, small-cell lung cancer, urothelial carcinoma, head, neck and breast cancer. The drug may stop the growth of cancer cells by targeting different cell proteins called fibroblast growth factor receptors (FGFR) that are needed for the survival of the cancer cells.

The primary objectives of the study are the continuation of rogaratinib treatment (as monotherapy or combination therapy) for patients after closure of their feeder studies and the further assessment of the safety of the drug.

The secondary objective is to investigate the tolerability of rogaratinib.

Roll-over Study to Continue Treatment With the Investigational Drug Rogaratinib and to Further Test Its Safety

A Roll-over Study to Provide Continued Treatment With Rogaratinib in Participants Who Were Enrolled in Rogaratinib Studies

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Atezolizumab

Cisplatin

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Part A: Part A is conducted in patients who are cisplatin-ineligible and have had no prior systemic treatment for locally advanced or metastatic disease.

Patients will receive rogaratinib plus atezolizumab combination treatment.

Part A:Rogaratinib will be administered orally until disease progression, unacceptable toxicity or consent withdrawal. The starting dose of 800 mg b.i.d. will be confirmed using a dose selection design.

Part A: A fixed dose of 1200 mg atezolizumab will be administered through intravenous (i.v.) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity or consent withdrawal.

FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study originally comprised two separate parts: Phase 1b (Part A) and Phase 2 (Part B). The study parts differ in design, objectives, and treatment.

The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability, RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients.

The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma.

Of note, patients who participate in Part A are not allowed to participate in Part B.

Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

Part B of the study will no longer be conducted.

Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma

An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

A DLT is defined as any of the hematological, non-hematological or other TEAEs occurring during Cycle 1 and regarded by the investigators and/or sponsor to be related to rogaratinib or atezolizumab. The CTCAE v 4.03 will be used to assess toxicities / adverse events.

Part A:Objective response rate (ORR) is defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response is not CR or PR, as well as patients without any post-baseline tumor assessment will be considered non-responders.

For all patients, the best overall tumor response will be determined locally by investigators using the RECIST criteria (v1.1).

Eligible patients will be selected based on the confirmation of high fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 mRNA expression levels in archival or fresh tumor biopsy specimens collected before the start of screening

Rogaratinib will be administered on 20 days in Cycle 1 (single dosing on Day 1 and twice daily dosing on Days 3-21). In Cycles ≥2, rogaratinib will be administered twice daily for 21 days, with cycles repeated every 21 days. Treatment will be continued until death, tumor progression, unacceptable toxicity, consent withdrawal, or until another criterion is met for withdrawal from the study at the discretion of the investigator.

This study is planned to determine the safety and tolerability of rogaratinib in Chinese patients with fibroblast growth factor receptor (FGFR)-positive refractory, locally advanced, or metastatic solid tumors and to characterize the pharmacokinetics of rogaratinib in Chinese patients.

Rogaratinib (BAY1163877) in Chinese Patients

An Open Label, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Rogaratinib (BAY1163877) in Chinese Patients With FGFR-positive Refractory, Locally Advanced, or Metastatic Solid Tumors

Response rate is defined as the proportion of patients who have a best overall response rating of complete response (CR) and partial response (PR) that is achieved during treatment.

Dose escalation:

The starting dose of the combination will be escalated in a stepwise fashion, escalating one drug at a time.

Dose expansion (urothelial cancer):

Patients in the dose expansion will be treated with the combination identified in the dose escalation part of the study.

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.

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.

Copanlisib (BAY80-6946)

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.

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

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

ORR in patients receiving the recommended dose of the rogaratinib-copanlisib-combination during the dose expansion part

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma	NCT03410693	Carcinoma, Tran...	Rogaratinib (BA... Chemotherapy	18 Years -	Bayer
Roll-over Study to Continue Treatment With the Investigational Drug Rogaratinib and to Further Test Its Safety	NCT04125693	Cancer	Rogaratinib (BA... Combination dru...	18 Years -	Bayer
Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma	NCT03473756	Urothelial Carc...	Rogaratinib (BA... Atezolizumab	18 Years -	Bayer
Rogaratinib (BAY1163877) in Chinese Patients	NCT03788603	Neoplasms	Rogaratinib (BA...	18 Years -	Bayer
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	NCT03517956	Advanced or Met...	Rogaratinib (BA... Copanlisib (BAY...	18 Years -	Bayer

Spots Global Cancer Trial Database for rogaratinib (bay1163877)