Derazantinib Alone or in Combination With Paclitaxel, Ram... | NCT04604132

NCT04604132

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily	Experimental	Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily	Drug: Derazantinib
Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily	Experimental	Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily	Drug: Derazantinib
Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily	Experimental	Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily	Drug: Derazantinib
Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab	Experimental	Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab	Drug: Derazantinib-paclitaxel-ramucirumab combination
Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab	Experimental	Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Derazantinib	Drug	Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1).	Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	From first dose and up to 18 months
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	From first dose and up to 4 months
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.	From first dose and up to 18 months

Secondary Outcomes

Measure	Description	Time Frame
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.	From first dose and up to 9 months
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts

Eligibility Module

Eligibility Criteria

Main inclusion criteria

Patients meeting all of the inclusion criteria at screening were eligible for enrollment in the study, including:

Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach.
Negative HER2 status obtained from the most recent available tissue sample.
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.
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.
Measurable disease as defined by the Investigator using RECIST 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
Adequate organ functions as indicated by Screening visit laboratory values.

Main exclusion criteria

Patients meeting any of the following exclusion criteria at screening were not eligible to be enrolled in the study:

Receipt of prior cancer treatment within specific interval periods.
For patients enrolled in Substudy 1, prior treatment with FGFR inhibitors.
For patients enrolled in Substudy 2, prior treatment with:
- Taxanes within 6 months prior to randomization
- FGFR inhibitors or pathway-targeting agents
- Anti-VEGF(R) therapeutic antibody or pathway-targeting agents
Concurrent evidence of clinically significant corneal or retinal disorder likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion (unless related to trauma), inflammation/ulceration, confirmed by ophthalmological examination.
History of clinically significant cardiac disorders, including myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug, and/or any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months of the first dose of study drug, and/or concurrent and clinically significant abnormalities on ECG at Screening, including QTcF > 450 ms for males or > 460 ms for females (mean values from triplicate ECGs).
Any unresolved (at the time of Screening) clinically significant CTCAE Grade ≥ 2 toxicity (except for alopecia, Grade ≤ 2 platinum-therapy related neuropathy, or Grade ≤ 2 anemia from previous anti-tumor treatment and/or from medical/surgical procedures/interventions).
Known central nervous system metastases.
Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration.
Significant gastrointestinal disorders that could interfere with the absorption, metabolism, or excretion of derazantinib.
History of additional malignancy that was progressing or required active treatment.

Name	Affiliation	Role
Manuel Häckl, MD	Basilea Pharmaceutica International Ltd, Allschwil	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AdventHealth Cancer Institute		Orlando	Florida	32806	United States
Memorial Sloan Kettering Cancer Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 21, 2021	Nov 21, 2023

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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).

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 18 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00013 OG0018

Title

Denominators

Categories

Title	Measurements
	OG0000.0(0.0 to 20.6) OG0010.0(0.0 to 31.2)

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

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).

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 4 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

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.

Posted

Number

From first dose and up to 18 months

ID	Title	Description
OG000	Substudy 2 Combined: Derazantinib +Paclitaxel+ Ramucirumab	Derazantinib-paclitaxel-ramucirumab combination: Derazantinib was administered orally at a dose of either 200 mg or 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.

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.

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 9 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 18 months

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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

Posted

Median

90% Confidence Interval

months

From first dose and up to 9 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Overall Survival (OS) in Substudy 1 in Cohort 1.3

OS was measured from patient enrollment to time of death.

The intent-to-treat (ITT) population comprised all patients enrolled and allocated to treatment, regardless of the administration of the study treatment.

Posted

Median

95% Confidence Interval

months

From first dose and up to 9 months

ID	Title	Description
OG000	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 Substudy 1.

Units	Counts
Participants	OG000

Secondary

OS in Substudy 2

OS was measured from patient enrollment to time of death

ITT population comprised all patients enrolled and allocated to treatment, regardless of the administration of the study treatment.

Posted

Median

95% Confidence Interval

months

From first dose and up to 15 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

ORR in Substudy 2

ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1.

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 15 months

ID	Title	Description
OG000	Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-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.
OG001	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.

Secondary

DCR in Substudy 2

Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1.

Posted

Number

90% Confidence Interval

Percentage of participants

From first dose and up to 15 months

ID	Title	Description
OG000	Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-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.
OG001	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.

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).

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)

Posted

Median

95% Confidence Interval

months

From first dose and up to 15 months

ID	Title	Description
OG000	Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-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.
OG001	Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-paclitaxel-ramucirumab combination: Derazantinib was administered orally at a dose of either 300 mg once daily or 200 mg twice 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.

Secondary

PFS in Substudy 2

PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1.

Posted

Median

90% Confidence Interval

months

From first dose and up to 15 months

ID	Title	Description
OG000	Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-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.
OG001	Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab	Derazantinib-paclitaxel-ramucirumab combination: Derazantinib was administered orally at a dose of 300 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.

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.

The Safety population comprises all patients who received at least one dose of study treatment (derazantinib, paclitaxel or ramucirumab).

Posted

Number

Counts of participants

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily	Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily	10	13	7	13	12	13
EG001	Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily	Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily	6	8	4	8	8	8
EG002	Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily	Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily	10	13	10	13	13	13
EG003	Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab	Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib 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.	4	6	4	6	6	6
EG004	Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab	Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib 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.	0	7	3	7	7	7

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG0031 events1 affected6 at risk EG0040 events0 affected7 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0022 events1 affected13 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Disease progression	General disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0012 events2 affected8 at risk EG0026 events6 affected13 at risk EG003
General physical health deterioration	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Hepatic cytolysis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0012 events2 affected8 at risk EG0026 events6 affected13 at risk EG0032 events2 affected6 at risk EG0047 events5 affected7 at risk
Amylase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0012 events2 affected8 at risk EG0029 events7 affected13 at risk EG003
Blood albumin decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0025 events5 affected13 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Blood creatinine increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Blood glucose increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected8 at risk EG0022 events2 affected13 at risk EG003
Blood phosphorus increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Blood potassium increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
C-reactive protein increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Lipase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Platelet count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Platelet count increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Protein total decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Transaminases increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Weight decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Weight increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
White blood cell count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0014 events4 affected8 at risk EG0024 events4 affected13 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0022 events2 affected13 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Syncope	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Diabetic retinopathy	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Dry eye	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Eyelid oedema	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Iridocyclitis	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Keratitis	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Punctate keratitis	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Visual impairment	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Ear congestion	Ear and labyrinth disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0013 events2 affected8 at risk EG0021 events1 affected13 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events1 affected8 at risk EG0022 events2 affected13 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Breath odour	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0024 events4 affected13 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0026 events5 affected13 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0024 events4 affected13 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Erosive oesophagitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Gingival swelling	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0005 events5 affected13 at risk EG0014 events4 affected8 at risk EG0026 events6 affected13 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0013 events3 affected8 at risk EG0024 events4 affected13 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0023 events3 affected13 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0012 events2 affected8 at risk EG0025 events4 affected13 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0011 events1 affected8 at risk EG0021 events1 affected13 at risk EG003
Hyperphosphatasaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Bronchitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Cytomegalovirus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Gingivitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Herpes virus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Thrombophlebitis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0014 events4 affected8 at risk EG0022 events2 affected13 at risk EG003
Chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Chills	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0013 events3 affected8 at risk EG0025 events5 affected13 at risk EG003
Feeling hot	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
General physical health deterioration	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Mucosal inflammation	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Oedema	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Hepatic cytolysis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected8 at risk EG0020 events0 affected13 at risk EG003
Bartholin's cyst	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003
Penile haemorrhage	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Adjustment disorder with depressed mood	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0021 events1 affected13 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0010 events0 affected8 at risk EG0020 events0 affected13 at risk EG003

ID	Term
D013274	Stomach Neoplasms
D000168	Acrocephalosyndactylia

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases
D003398	Craniosynostoses
D013580	Synostosis
D004413	Dysostoses
D001848	Bone Diseases, Developmental
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D013576	Syndactyly
D019465	Craniofacial Abnormalities
D009139	Musculoskeletal Abnormalities
D017880	Limb Deformities, Congenital
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities