Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Mitogens

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients with urothelial cancer were treated with derazantinib 300 mg once daily

Patients with any solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as intravenous (IV) infusion

Patients with any solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Patients with FGFR inhibitor resistant urothelial cancer were treated with derazantinib 300 mg once daily

Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily

Derazantinib was administered orally at a dose of 300 mg once daily

Derazantinib 300 mg once daily monotherapy

Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Derazantinib 200 mg once daily + atezolizumab 1200 mg

Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Derazantinib 300 mg once daily+ atezolizumab 1200 mg

Derazantinib was administered orally at a dose of 200 mg twice daily in combination with atezolizumab 1200 mg every 3 weeks

Derazantinib 200 mg twice daily + atezolizumab 1200 mg

Derazantinib 300 mg once daily monotherapy (QD)

Derazantinib 300 mg once daily + atezolizumab 1200 mg

Derazantinib was administered orally at a dose of 200 mg twice daily

Derazantinib 200 mg twice daily monotherapy

Manuel Häckl, MD

The purpose of this study was to evaluate efficacy of derazantinib monotherapy or derazantinib-atezolizumab in combination in patients with advanced urothelial cancer harboring fibroblast growth factor receptor (FGFR) genetic aberrations (GA) of various clinical stages of disease progression and prior treatments.

The study comprised five open-label substudies (1-5) in patients with advanced urothelial cancer harboring FGFR GA (with the exception of substudy 2 which did not require a FGFR GA) who were treated by derazantinib monotherapy or derazantinib in combination with atezolizumab. The study enrolled patients with cisplatin-ineligible status, or patients whose disease progressed after either first-line treatment or prior treatment with FGFR inhibitors.

Derazantinib and Atezolizumab in Patients With Urothelial Cancer

An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations

ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded investigator central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1

The RP2D was determined by a joint decision taken by the Independent Data Monitoring Committee (IDMC), Investigators, and the Sponsor in reviewing the aggregate of DLT and AE data, and considering efficacy data

In Substudy 2, the primary endpoint was the number of patients with DLTs. A DLT was defined as a clinically-significant adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications. Any DLT had to be a toxicity considered at least possibly related to derazantinib or the combination of derazantinib and atezolizumab

DCR was defined as the proportion of patients who achieved a confirmed clinical response (CR), partial response (PR) or stable disease (SD) by BICR using the internationally recognized criteria in accordance with RECIST Version 1.1

DOR was calculated from the first date of documented tumor response (confirmed CR or PR) to the date of disease progression as assessed by BICR or death per RECIST 1.1

PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first

OS was calculated from the date of cohort assignment until death from any cause

Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 )

Basilea Pharmaceutica

Patients with urothelial cancer were treated with derazantinib 300 mg once daily

Derazantinib 300 mg once daily monotherapy: Derazantinib was administered orally at a dose of 300 mg once daily

Substudy 1: Derazantinib 300 mg Once Daily

Patients with solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 200 mg once daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg

Patients with solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 300 mg once daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 200 mg twice daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 200 mg twice daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg

Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily

Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 300 mg once daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily

Derazantinib 200 mg twice daily monotherapy: Derazantinib was administered orally at a dose of 200 mg twice daily

Substudy 5: Derazantinib 200 mg Twice Daily

Patients with solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 200 mg once daily+ atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg

Patients with solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 300 mg once daily+ atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily+ Atezolizumab 1200 mg

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Bladder

Renal pelvis

Ureter

Missing

Other site of primary tumor

Site of primary tumor at diagnosis

Scale 0

Scale 1

Scale 2

The ECOG PS scale indicates increasing levels of disability, with 0 indicating fully active; 1, restricted in strenuous activity; 2, restricted in work activity but ambulatory and capable of self-care

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

One treatment

Two treatments

Three or more treatments

No treatment

Number of previous anti-cancer treatments

Prior immune checkpoint inhibitor treatment

Treatment completed

Progressive disease

Toxicity

Other

Unknown

No previous therapy

Reason previous therapy ended

Study Director

Efficacy analyses were performed using the modified Intent-to-Treat (mITT) population: all patients who received at least one dose of derazantinib or atezolizumab, and had at least one post-baseline imaging assessment in accordance with RECIST 1.1, or documented clinical progression

Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)

Patients with solid tumors were treated with derazantinib 200 mg or 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Substudy 2 Combined (Dose-Level 1 and 2): Derazantinib 200 or 300 Once Daily+ Atezolizumab 1200 mg

The safety/intent-to-treat (ITT) population consisted of all patients who received at least one dose of derazantinib or atezolizumab

Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)

The maximum tolerated dose (MTD)-determining population included all patients enrolled in the MTD Part of each dose level who met the following minimum criteria during the DLT period:

* received at least one dose of derazantinib and atezolizumab and has experienced a DLT;
* received ≥ 90% of the derazantinib and atezolizumab dose, respectively, in Cycle 1 and did not experience a DLT, have been observed for ≥ 21 days following the first dose, and have been evaluated for safety

Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2

Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies

Duration of Response (DOR) Per RECIST 1.1

Efficacy analyses were performed using the modified Intent-to-Treat (mITT) population: all patients who received at least one dose of derazantinib or atezolizumab, and had at least one post-baseline imaging assessment in accordance with RECIST 1.1, or documented clinical progression.

ORR Based on RECIST 1.1 (Substudy 2)

Progression-free Survival (PFS) by RECIST in All Substudies

Overall Survival (OS) in All Substudies

Number of Patients With at Least Grade 3 Adverse Events (AEs)

Patients with solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as intravenous (IV) infusion

Derazantinib 200 mg once daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Derazantinib 300 mg once daily + atezolizumab 1200 mg: Derazantinib was administered orally at a dose o f 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

Overall Study

Digestive System Diseases

Cholangiocarcinoma

Liver Neoplasms

Adenocarcinoma

Bile Duct Cancer

Biliary Tract Cancer

Intrahepatic Cholangiocarcinoma

Crouzon Syndrome

Jackson-Weiss Syndrome

Pfeiffer Syndrome

Hematinics

Amino Acids

Liver Extracts

Tyrosine Kinase Inhibitors

Tyrosine

Patients who received derazantinib orally at dose levels from 25 mg every other day (QOD) - 200 mg daily (QD) on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.

Derazantinib low dose range

Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.

Derazantinib middle dose range

Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.

Derazantinib high dose range

Derazantinib was administered orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule.

Derazantinib at recommended phase 2 dose (RP2D)

Marc Engelhardt, MD

This was an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (Part 1; Dose Escalation/Food-effect Cohorts) or with advanced solid tumors with FGFR genetic aberrations, including iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding).

Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations

A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion

Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE)

The number of patients with an objective tumor response, which included those with either a complete response (CR) or a partial response (PR) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response.

The objective response rate (ORR) was defined as the proportion of patients with a CR or PR.

The number of patients with tumor disease control, which included those with either a complete or partial tumor response, or a stable disease (SD) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The disease control rate (DCR) was defined as the proportion of patients with CR, PR or SD.

PFS was calculated as the time from the date of first dose until documented radiographic disease progression or death from any cause, whichever occurred first. Disease progression is measured according to a specified radiologic increase in tumor size.

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group

Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group

Derazantinib 400 mg QOD - 425 mg QD - High Dose Group

Derazantinib 300 mg QD - Expanded Cohort Group

Derazantinib 250 mg QOD - 325 mg QD - Middle Dose Group

Age, Categorical

Ethnicity (NIH/OMB)

Safety Population (patients who received any amount of derazantinib)

The safety population included all subjects who received at least one dose of derazantinib.

Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)

Evaluable Population: patients who received at least one cycle of study treatment and had at least one postbaseline tumor evaluation.

Proportion of Patients With an Objective Tumor Response Per RECIST 1.1

Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria .

Proportion of Patients With Disease Control Per RECIST 1.1

Progression-free Survival (PFS)

Subjects who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Subjects who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Subjects who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Subjects who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Derazantinib and Atezolizumab in Patients With Urothelial Cancer	NCT04045613	Urothelial Carc...	Derazantinib 30... Derazantinib 20... Derazantinib 30... Derazantinib 20... Derazantinib 30... Derazantinib 30... Derazantinib 20...	18 Years -	Basilea Pharmaceutica
Derazantinib and Atezolizumab in Patients With Urothelial Cancer	NCT04045613	Urothelial Carc...	Derazantinib 30... Derazantinib 20... Derazantinib 30... Derazantinib 20... Derazantinib 30... Derazantinib 30... Derazantinib 20...	18 Years -	Basilea Pharmaceutica
Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations	NCT01752920	Solid Tumor	Derazantinib lo... Derazantinib mi... Derazantinib hi... Derazantinib at...	18 Years -	Basilea Pharmaceutica

Spots Global Cancer Trial Database for fgfr genetic aberration