Gastric Adenocarcinoma
Conditions
Keywords
gastric cancer, gastro-esophageal adenocarcinoma, adenocarcinoma of the stomach or gastro-esophageal junction, fibroblast growth factor receptor, FGFR genetic aberration, targeted therapy, derazantinib, atezolizumab, Tecentriq, paclitaxel, ramucirumab, Cyramza, solid tumor
Brief summary
The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. with human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring fibroblast growth factor receptor 2 (FGFR2) genetic aberrations (GA).
Detailed description
The study comprised two open-label substudies in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 gene translocations, FGFR2 gene amplifications, or FGFR1-3 mutations. In Substudy 1, GAC patients with specified FGFR GAs, after either first- or second-line treatment, and no approved treatment alternative were treated with derazantinib 300 mg once daily or 200 mg twice daily, with the aim of evaluating the safety, tolerability, and efficacy of derazantinib monotherapy in this patient population. In Substudy 2, GAC patients with specified FGFR GAs after standard first-line treatment, were treated with a derazantinib-paclitaxel-ramucirumab combination with the aim of evaluating the safety, tolerability, and efficacy of the combination therapy and determining the recommended phase 2 dose (RP2D). The study originally planned to include three substudies but was prematurely terminated for administrative reasons before the third substudy (including combination therapy with derazantinib plus atezolizumab) was initiated.
Interventions
DRUGDerazantinib
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1).
DRUGDerazantinib-paclitaxel-ramucirumab combination
Derazantinib was administered orally at a dose of 200 mg once daily in combination with paclitaxel and ramucirumab. Paclitaxel was administered intravenously at a dose of 80 mg/m² on days 1, 8, and 15 of a 28-day cycle in combination with ramucirumab. Ramucirumab was administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel.
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
Main inclusion criteria Patients meeting all of the inclusion criteria at screening were eligible for enrollment in the study, including: 1. Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach. 2. Negative HER2 status obtained from the most recent available tissue sample. 3. Inoperable recurrent, locally advanced adenocarcinoma or progressing stage IV adenocarcinoma of the gastro-esophageal junction or stomach, and prior anti-tumor treatment as specified for each Substudy. Patients were required to be staged as inoperable at the time of screening in order to avoid interference of any potentially planned surgery with RECIST requirements during the study: Substudy 1: Patients with radiographically documented disease progression after either standard first- or second-line treatment, and no approved and/or tolerable treatment alternative. Substudy 2: Patients with radiographically documented disease progression after standard first-line treatment, and per Investigator assessment considered suitable to tolerate the treatment regimen. 4. Eligible FGFRfus/amp/mt positive test result. For Substudy 1 Cohort 1.1, FGFR2fus/amp; for Cohort 1.2, FGFR1-3mt; for Cohort 1.3, FGFRfus/amp/mt. For Substudy 2, FGFRfus/amp/mt. 5. Measurable disease as defined by the Investigator using RECIST 1.1 criteria 6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 7. Adequate organ functions as indicated by Screening visit laboratory values. Main
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2) | From first dose and up to 18 months | ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means \>=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR. The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2. |
| Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3 | From first dose and up to 4 months | PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC |
| Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination) | From first dose and up to 18 months | RP2D was determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Substudy 1 in Cohort 1.3 | From first dose and up to 9 months | OS was measured from patient enrollment to time of death. |
| OS in Substudy 2 | From first dose and up to 15 months | OS was measured from patient enrollment to time of death |
| ORR in Substudy 2 | From first dose and up to 15 months | ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1. |
| ORR in Substudy 1 in Cohort 1.3 | From first dose and up to 9 months | ORR was defined by the percentage of patients with CR or PR by BICR according to RECIST Version 1.1. |
| DOR in Substudy 2 (Separate and Combined Cohorts) | From first dose and up to 15 months | DOR was calculated from the first date of documented tumor response to disease progression by BICR per RECIST version 1.1 (or death if no documentation of PD is obtained). |
| PFS in Substudy 2 | From first dose and up to 15 months | PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1. |
| Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | TEAEs defined as AEs which were assessed per patient from the patient's first dose and until 90 days after the last dose, which corresponded up to 19 months | Number of patients experiencing TEAE of Grade 3 and above according to Common Terminology Criteria for Adverse Events (CTCAE). CTCAE are a set of criteria for the standardized classification of TEAEs of drugs used in cancer therapy. It uses a range of grades from 1 to 5 describing increasing levels of severity of the TEAEs. |
| DCR in Substudy 2 | From first dose and up to 15 months | Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1. |
| Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts | From first dose and up to 18 months | Defined as the percentage of patients with confirmed CR, PR or stable disease (SD) by BICR per RECIST version 1.1. |
| PFS in Substudy 1 in Cohort 1.3 | From first dose and up to 9 months | PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1 |
Countries
Argentina, Australia, Belgium, Brazil, Chile, France, Germany, Italy, Poland, Russia, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
From 6 Oct. 2020 to 10 Jun. 2022, 919 patients (pt.) had molecular pre-screening. 66 had clinical screening, and 47 were treated. In Substudy 2, pt. were allocated to 1 of 3 dose levels using a dose escalation scheme: Derazantinib at a dose of 200 mg once daily, 300 mg once daily, or 200 mg twice daily, all in combination with paclitaxel and ramucirumab. However, no pt. received the highest dose, therefore only the 200 and 300 mg once daily dose levels are presented in the results section.
Participants by arm
| Arm | Count |
|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1. | 13 |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1. | 8 |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily Derazantinib was administered orally at a dose of 200 mg twice daily as monotherapy in the Substudy 1. | 13 |
| Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab Derazantinib-paclitaxel-ramucirumab combination: Derazantinib was administered orally at a dose of 200 mg in combination with paclitaxel and ramucirumab.
Paclitaxel was administered intravenously at a dose of 80 mg/m² on days 1, 8, and 15 of a 28-day cycle in combination with ramucirumab.
Ramucirumab was administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel. | 6 |
| Substudy 2: Derazantinib 300 mg Once Daily+Paclitaxel+ Ramucirumab Derazantinib-paclitaxel-ramucirumab combination: Derazantinib was administered orally at a dose of 300 mg once daily in combination with paclitaxel and ramucirumab.
Paclitaxel was administered intravenously at a dose of 80 mg/m² on days 1, 8, and 15 of a 28-day cycle in combination with ramucirumab.
Ramucirumab was administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel. | 7 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 1 | 2 |
| Overall Study | Death | 3 | 1 | 2 | 1 | 0 |
| Overall Study | Progressive disease: Clinical progression | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive disease: Radiological progression | 8 | 7 | 10 | 4 | 3 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab | Substudy 2: Derazantinib 300 mg Once Daily+Paclitaxel+ Ramucirumab | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 10.77 | 66.1 years STANDARD_DEVIATION 9.39 | 54.8 years STANDARD_DEVIATION 13.43 | 55.2 years STANDARD_DEVIATION 10.53 | 52.0 years STANDARD_DEVIATION 11.34 | 59.3 years STANDARD_DEVIATION 12.43 |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 7 Participants | 9 Participants | 6 Participants | 5 Participants | 36 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 12 Participants | 5 Participants | 2 Participants | 33 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 13 | 6 / 8 | 10 / 13 | 4 / 6 | 0 / 7 |
| other Total, other adverse events | 12 / 13 | 8 / 8 | 13 / 13 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 7 / 13 | 4 / 8 | 10 / 13 | 4 / 6 | 3 / 7 |
Outcome results
Primary
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means \>=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR. The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2.
Time frame: From first dose and up to 18 months
Population: Modified intent-to-treat (mITT) population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2) | 0.0 Percentage of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2) | 0.0 Percentage of participants |
Primary
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC
Time frame: From first dose and up to 4 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3 | 7.7 Percentage of participants |
Primary
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
RP2D was determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC.
Time frame: From first dose and up to 18 months
Population: The Maximum Tolerated Dose (MTD)-determining population comprised all patients enrolled in Substudy 2 who meet the minimum criteria during the first 28-day treatment cycle (Cycle 1):~* received at least one dose of derazantinib-paclitaxel-ramucirumab in combination and has experienced a DLT~* or~* received ≥ 80% of the derazantinib-paclitaxel-ramucirumab dose, respectively, in Cycle 1 and, had been observed for ≥ 28 days following the first dose, and had been evaluated for safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination) | 200 mg |
Secondary
DCR in Substudy 2
Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1.
Time frame: From first dose and up to 15 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | DCR in Substudy 2 | 80.0 Percentage of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | DCR in Substudy 2 | 71.4 Percentage of participants |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | DCR in Substudy 2 | 75.0 Percentage of participants |
Secondary
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts
Defined as the percentage of patients with confirmed CR, PR or stable disease (SD) by BICR per RECIST version 1.1.
Time frame: From first dose and up to 18 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts | 30.8 Percentage of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts | 25.0 Percentage of participants |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts | 15.4 Percentage of participants |
| Substudy 1 Combined: Derazantinib 300 mg Once Daily or 200 mg Twice Daily | Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts | 23.5 Percentage of participants |
Secondary
DOR in Substudy 2 (Separate and Combined Cohorts)
DOR was calculated from the first date of documented tumor response to disease progression by BICR per RECIST version 1.1 (or death if no documentation of PD is obtained).
Time frame: From first dose and up to 15 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).~Within the mITT, only patients with confirmed CR or PR have been considered for this endpoint (2 and 4 patients from the 200 mg and 300 mg arm, respectively)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | DOR in Substudy 2 (Separate and Combined Cohorts) | 9.2 months |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | DOR in Substudy 2 (Separate and Combined Cohorts) | NA months |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | DOR in Substudy 2 (Separate and Combined Cohorts) | 9.2 months |
Secondary
Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)
Number of patients experiencing TEAE of Grade 3 and above according to Common Terminology Criteria for Adverse Events (CTCAE). CTCAE are a set of criteria for the standardized classification of TEAEs of drugs used in cancer therapy. It uses a range of grades from 1 to 5 describing increasing levels of severity of the TEAEs.
Time frame: TEAEs defined as AEs which were assessed per patient from the patient's first dose and until 90 days after the last dose, which corresponded up to 19 months
Population: The Safety population comprises all patients who received at least one dose of study treatment (derazantinib, paclitaxel or ramucirumab).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with only unrelated TEAEs of Grade 3 or above | 9 Counts of participants |
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients without TEAEs of Grade 3 or above | 4 Counts of participants |
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with related TEAEs of Grade 3 or above | 0 Counts of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with related TEAEs of Grade 3 or above | 3 Counts of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with only unrelated TEAEs of Grade 3 or above | 3 Counts of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients without TEAEs of Grade 3 or above | 2 Counts of participants |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with related TEAEs of Grade 3 or above | 6 Counts of participants |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with only unrelated TEAEs of Grade 3 or above | 5 Counts of participants |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients without TEAEs of Grade 3 or above | 2 Counts of participants |
| Substudy 1 Combined: Derazantinib 300 mg Once Daily or 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with only unrelated TEAEs of Grade 3 or above | 1 Counts of participants |
| Substudy 1 Combined: Derazantinib 300 mg Once Daily or 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients without TEAEs of Grade 3 or above | 1 Counts of participants |
| Substudy 1 Combined: Derazantinib 300 mg Once Daily or 200 mg Twice Daily | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with related TEAEs of Grade 3 or above | 4 Counts of participants |
| Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with related TEAEs of Grade 3 or above | 6 Counts of participants |
| Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients with only unrelated TEAEs of Grade 3 or above | 1 Counts of participants |
| Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab | Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) | Number of patients without TEAEs of Grade 3 or above | 0 Counts of participants |
Secondary
ORR in Substudy 1 in Cohort 1.3
ORR was defined by the percentage of patients with CR or PR by BICR according to RECIST Version 1.1.
Time frame: From first dose and up to 9 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | ORR in Substudy 1 in Cohort 1.3 | 0.0 Percentage of participants |
Secondary
ORR in Substudy 2
ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1.
Time frame: From first dose and up to 15 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | ORR in Substudy 2 | 40.0 Percentage of participants |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | ORR in Substudy 2 | 57.1 Percentage of participants |
Secondary
OS in Substudy 2
OS was measured from patient enrollment to time of death
Time frame: From first dose and up to 15 months
Population: ITT population comprised all patients enrolled and allocated to treatment, regardless of the administration of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | OS in Substudy 2 | 5.5 months |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | OS in Substudy 2 | NA months |
Secondary
Overall Survival (OS) in Substudy 1 in Cohort 1.3
OS was measured from patient enrollment to time of death.
Time frame: From first dose and up to 9 months
Population: The intent-to-treat (ITT) population comprised all patients enrolled and allocated to treatment, regardless of the administration of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | Overall Survival (OS) in Substudy 1 in Cohort 1.3 | 3.3 months |
Secondary
PFS in Substudy 1 in Cohort 1.3
PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1
Time frame: From first dose and up to 9 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | PFS in Substudy 1 in Cohort 1.3 | 1.7 months |
Secondary
PFS in Substudy 2
PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1.
Time frame: From first dose and up to 15 months
Population: mITT population: all patients who received at least one dose of derazantinib and had at least one post-baseline imaging assessment in accordance with RECIST 1.1 or documented clinical progression or died from any cause on or after the first dose of study treatment and until safety follow-up visit (inclusive).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily | PFS in Substudy 2 | 11.1 months |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily | PFS in Substudy 2 | NA months |