Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter. Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated. The dosage in the phase 2 portion will be the MTD/RP2D determined in the phase 1b portion.

Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter.

Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated.

Debio 1347

Komal Jhaveri, MD FACP

The purpose of a phase Ib study is to find out the best or maximum tolerated dose of a medication or combination of medications. Therefore, the purpose of this study is to decide the best dose of the study drug, Debio 1347, that can be given in combination with the standard hormonal drug, fulvestrant. Debio 1347 and fulvestrant could shrink the cancer but it could also cause side effects. This study tells us about the side effects of these drugs when given in this new combination, and how often they occur.

This is an open-label, single institution, phase Ib/phase II non-randomized trial.

A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer

A Phase Ib/II Study of Debio 1347 Plus Fulvestrant in Patients With FGFR-Amplified Endocrine Receptor Positive Metastatic Breast Cancer

Selected non-hematologic and hematologic toxicities, as measured by the NCI CTCAE Version 4.0, will be described by frequency and grade, by cycle and over all cycles, with the maximum grade over all cycles used as the summary measure per patient.

Tumor response is based on the RECIST v.1.1.

Debiopharm International SA

Memorial Sloan Kettering Cancer Center

All participants received starting dose of Debio 1347 of 80mg, de-escalation cohort did not occur

Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter. Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated. The dosage in the phase 2 portion will be the MTD/RP2D determined in the phase 1b portion.

Fulvestrant: Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter.

Debio 1347: Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated.

Cohort 1: Fulvestrant and Debio 1347

Cohort 2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Komal Jhaveri MD

Number of Patients Experiencing Dose Limiting Toxicity

Proportion of Patients Who Have a Best Overall Response

Cohort 2: Expansion

Overall Study

Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).

Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).

Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).

The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.

Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)

A Phase II Basket Study of the Oral Selective Pan-FGFR Inhibitor Debio 1347 in Subjects With Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3

ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.

OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.

An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Geometric mean and geometric percent CV summary was estimated based on log-linear model.

Caris Life Sciences

Optimal Research (Just In Time sites)

Safety Population consisted of all participants who received study drug. The all-cause mortality is reported for all participants enrolled in the study and who completed the study visits.

Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).

Cohort 1: Debio 1347 (Biliary Tract Cancer)

Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks)

Cohort 2: Debio 1347 (Urothelial Cancer)

Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)

White

Black or African American

Asian

Not Willing to Provide

Other

Race/Ethnicity, Customized

Intent-to-treat (ITT) Population consisted of all participants who received study drug.

Limitations of the trial such as small numbers of participants analyzed or technical problems leading to unreliable data.

Due to the premature termination of participant recruitment and shortened follow-up, the primary efficacy analysis was likely underpowered in the final analysis, leading to greater statistical uncertainty in results.

Head Clinical Research & Development

Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).

ITT Population consisted of all participants who received study drug. Overall number of participants analyzed is the number of participants with measurable disease and tumor assessment at Baseline.

Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria

ITT Population consisted of all participants who received study drug. Only participants with best overall response of CR or PR were analyzed for this endpoint.

Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC)

ITT population consisted of all participants who received study drug. Percentages are rounded off to the nearest single decimal point.

Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC)

ITT population consisted of all participants who received study drug.

Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC)

Overall Survival (OS)

TEAEs

Serious TEAEs

Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, once daily QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).

Safety Population consisted of all participants who received study drug.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)

Pharmacokinetic (PK) Population included participants who received one or more doses of Debio 1347 and have at least one PK concentration result available. Overall number of participants analyzed is the number of participants with data available for analysis.

Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma

PK Population included participants who received one or more doses of Debio 1347 and have at least one PK concentration result available. Overall number of participants analyzed is the number of participants with data available for analyses.

Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma

The study was terminated by sponsor and thus the analysis for this outcome measure was not deemed necessary and no data was collected.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer	NCT03344536	Breast Cancer	Fulvestrant Debio 1347	18 Years -	Memorial Sloan Kettering Cancer Center
Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)	NCT03834220	Solid Tumor	Debio 1347	18 Years -	Debiopharm International SA
A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer	NCT03344536	Breast Cancer	Fulvestrant Debio 1347	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for debio 1347

Every month we try and update this database with for debio 1347 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for debio 1347

Every month we try and update this database with for debio 1347 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for debio 1347 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.