Urothelial Carcinoma
Conditions
Keywords
metastatic urothelial cancer, bladder cancer, Fibroblast Growth Factor Receptor, FGFR genetic aberration, targeted therapy, derazantinib, checkpoint inhibitor, immune checkpoint blockade, atezolizumab, Tecentriq, solid tumor
Brief summary
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.
Detailed description
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.
Interventions
DRUGDerazantinib 300 mg once daily monotherapy
Derazantinib was administered orally at a dose of 300 mg once daily
DRUGDerazantinib 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
DRUGDerazantinib 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
DRUGDerazantinib 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
DRUGDerazantinib 300 mg once daily monotherapy (QD)
Derazantinib was administered orally at a dose of 300 mg once daily
DRUGDerazantinib 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
DRUGDerazantinib 200 mg twice daily monotherapy
Derazantinib was administered orally at a dose of 200 mg twice daily
Sponsors
Basilea Pharmaceutica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract * Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease * Documented central FGFR genetic aberration (FGFR1, FGFR2, or FGFR3 mutations / short variants and rearrangements / fusions) (Note; Substudy 2 started with patients requiring an FGFR GA, but this requirement was removed from the protocol later on) * Measurable disease, as defined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 * Adequate organ functions as indicated by Screening visit local laboratory values
Exclusion criteria
* Receipt of prior cancer treatment within specific interval periods * Concurrent evidence of any clinically significant corneal or retinal disorder * History of clinically significant cardiac disorders * Known CNS metastases * Concurrent uncontrolled or active infection with human immunodeficiency virus * Active hepatitis B or chronic hepatitis B without current antiviral therapy * Active hepatitis C * Active tuberculosis * Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | From first dose up to 2 years | 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 |
| Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2) | From first dose up to 2 years | 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 |
| Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2 | From first dose up to 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) by RECIST in All Substudies | From first dose up to 2 years | PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first |
| Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | From first dose up to 2 years | 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 |
| Number of Patients With at Least Grade 3 Adverse Events (AEs) | From first dose and until 90 days following the last dose | Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 ) |
| Overall Survival (OS) in All Substudies | From first dose up to 2 years | OS was calculated from the date of cohort assignment until death from any cause |
| Duration of Response (DOR) Per RECIST 1.1 | From first dose up to 2 years | 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 |
| ORR Based on RECIST 1.1 (Substudy 2) | From first dose up to 2 years | 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 |
Countries
Australia, Austria, Canada, Czechia, France, Germany, Hungary, Italy, Poland, South Korea, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
From August, 2019 to September, 2022, 321 patients underwent molecular screening, 131 underwent clinical screening, and 95 entered the study and were assigned treatment
Participants by arm
| Arm | Count |
|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily 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 | 32 |
| Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg 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 | 14 |
| Substudy 2 (Dose-Level 2): Derazantinib 300 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 | 12 |
| Substudy 3: Derazantinib 200 mg Twice 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 | 2 |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily 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 | 8 |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg 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 | 10 |
| Substudy 5: Derazantinib 200 mg Twice Daily 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 | 17 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Death | 3 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other reasons | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive disease: Clinical progression | 1 | 0 | 3 | 1 | 1 | 3 | 3 |
| Overall Study | Progressive disease: Radiological progression | 24 | 6 | 8 | 0 | 6 | 6 | 11 |
| Overall Study | Withdrawal by Subject | 0 | 5 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Substudy 1: Derazantinib 300 mg Once Daily | Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg | Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily+ Atezolizumab 1200 mg | Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Substudy 5: Derazantinib 200 mg Twice Daily |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 11.63 | 68.4 years STANDARD_DEVIATION 10.17 | 65.6 years STANDARD_DEVIATION 9.84 | 53.3 years STANDARD_DEVIATION 12.58 | 67.5 years STANDARD_DEVIATION 12.02 | 66.6 years STANDARD_DEVIATION 11.94 | 62.7 years STANDARD_DEVIATION 16.1 | 64.2 years STANDARD_DEVIATION 7.61 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Scale 0 | 31 Participants | 14 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 8 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Scale 1 | 55 Participants | 15 Participants | 8 Participants | 9 Participants | 1 Participants | 6 Participants | 7 Participants | 9 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Scale 2 | 9 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Number of previous anti-cancer treatments No treatment | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of previous anti-cancer treatments One treatment | 20 Participants | 5 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 7 Participants |
| Number of previous anti-cancer treatments Three or more treatments | 51 Participants | 18 Participants | 6 Participants | 5 Participants | 1 Participants | 8 Participants | 9 Participants | 4 Participants |
| Number of previous anti-cancer treatments Two treatments | 23 Participants | 9 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Prior immune checkpoint inhibitor treatment | 61 Participants | 26 Participants | 1 Participants | 4 Participants | 0 Participants | 8 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 9 Participants | 1 Participants | 5 Participants | 0 Participants | 3 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 58 Participants | 18 Participants | 12 Participants | 5 Participants | 2 Participants | 2 Participants | 7 Participants | 12 Participants |
| Reason previous therapy ended No previous therapy | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Reason previous therapy ended Other | 5 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Reason previous therapy ended Progressive disease | 71 Participants | 23 Participants | 10 Participants | 12 Participants | 0 Participants | 6 Participants | 8 Participants | 12 Participants |
| Reason previous therapy ended Toxicity | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Reason previous therapy ended Treatment completed | 10 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Reason previous therapy ended Unknown | 5 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 38 Participants | 11 Participants | 4 Participants | 8 Participants | 1 Participants | 4 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 57 Participants | 21 Participants | 10 Participants | 4 Participants | 1 Participants | 4 Participants | 4 Participants | 13 Participants |
| Site of primary tumor at diagnosis Bladder | 49 Participants | 19 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants | 7 Participants | 11 Participants |
| Site of primary tumor at diagnosis Missing | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Site of primary tumor at diagnosis Other site of primary tumor | 22 Participants | 0 Participants | 12 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Site of primary tumor at diagnosis Renal pelvis | 15 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Site of primary tumor at diagnosis Ureter | 8 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 32 | 3 / 14 | 3 / 12 | 1 / 2 | 0 / 8 | 4 / 10 | 1 / 17 |
| other Total, other adverse events | 30 / 32 | 14 / 14 | 12 / 12 | 2 / 2 | 8 / 8 | 10 / 10 | 17 / 17 |
| serious Total, serious adverse events | 17 / 32 | 4 / 14 | 6 / 12 | 1 / 2 | 3 / 8 | 6 / 10 | 8 / 17 |
Outcome results
Primary
Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2
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
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2 | 0 participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2 | 0 participants |
Primary
Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)
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
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | 9.4 Percentage of participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | 0.0 Percentage of participants |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | 14.3 Percentage of participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | 0.0 Percentage of participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) | 5.9 Percentage of participants |
Primary
Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)
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
Time frame: From first dose up to 2 years
Population: The safety/intent-to-treat (ITT) population consisted of all patients who received at least one dose of derazantinib or atezolizumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2) | 300 mg |
Secondary
Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies
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
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 18.8 Percentage of participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 18.2 Percentage of participants |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 50.0 Percentage of participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 50.0 Percentage of participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 28.6 Percentage of participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 20.0 Percentage of participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies | 52.9 Percentage of participants |
Secondary
Duration of Response (DOR) Per RECIST 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
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Duration of Response (DOR) Per RECIST 1.1 | 6.9 months |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Duration of Response (DOR) Per RECIST 1.1 | NA months |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Duration of Response (DOR) Per RECIST 1.1 | 7.4 months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Duration of Response (DOR) Per RECIST 1.1 | NA months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Duration of Response (DOR) Per RECIST 1.1 | 3.3 months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Duration of Response (DOR) Per RECIST 1.1 | NA months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Duration of Response (DOR) Per RECIST 1.1 | NA months |
Secondary
Number of Patients With at Least Grade 3 Adverse Events (AEs)
Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 )
Time frame: From first dose and until 90 days following the last dose
Population: The safety/intent-to-treat (ITT) population consisted of all patients who received at least one dose of derazantinib or atezolizumab
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 10 Participants |
| Substudy 1: Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 11 Participants |
| Substudy 1: Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 11 Participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 3 Participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 5 Participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 6 Participants |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 3 Participants |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 7 Participants |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 2 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 0 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 2 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 0 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 2 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 2 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 4 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 5 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 4 Participants |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 1 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with only unrelated CTCAE Grade ≥3 | 3 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients without CTCAE Grade ≥3 | 5 Participants |
| Substudy 5: Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Adverse Events (AEs) | Number of patients with related CTCAE Grade ≥3 | 9 Participants |
Secondary
ORR Based on RECIST 1.1 (Substudy 2)
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
Time frame: From first dose up to 2 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | ORR Based on RECIST 1.1 (Substudy 2) | 0.0 Percentage of participants |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | ORR Based on RECIST 1.1 (Substudy 2) | 16.7 Percentage of participants |
Secondary
Overall Survival (OS) in All Substudies
OS was calculated from the date of cohort assignment until death from any cause
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Overall Survival (OS) in All Substudies | 4.7 months |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Overall Survival (OS) in All Substudies | 8.7 months |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Overall Survival (OS) in All Substudies | 12.6 months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Overall Survival (OS) in All Substudies | 4.2 months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Overall Survival (OS) in All Substudies | NA months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Overall Survival (OS) in All Substudies | 6.2 months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Overall Survival (OS) in All Substudies | 7.5 months |
Secondary
Progression-free Survival (PFS) by RECIST in All Substudies
PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first
Time frame: From first dose up to 2 years
Population: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Derazantinib 300 mg Once Daily | Progression-free Survival (PFS) by RECIST in All Substudies | 2.0 months |
| Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg | Progression-free Survival (PFS) by RECIST in All Substudies | 2.0 months |
| Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily | Progression-free Survival (PFS) by RECIST in All Substudies | 4.2 months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Progression-free Survival (PFS) by RECIST in All Substudies | 2.5 months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Progression-free Survival (PFS) by RECIST in All Substudies | 2.0 months |
| Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg | Progression-free Survival (PFS) by RECIST in All Substudies | 1.9 months |
| Substudy 5: Derazantinib 200 mg Twice Daily | Progression-free Survival (PFS) by RECIST in All Substudies | 2.1 months |