FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma

Sponsor

Basilea Pharmaceutica (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04604132

Collaborator

(none)

Enrollment

Locations

Arms

32.8

Anticipated Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations (GA).

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma	Drug: Derazantinib Drug: Derazantinib-paclitaxel-ramucirumab Drug: Derazantinib-atezolizumab Drug: Paclitaxel-ramucirumab	Phase 1/Phase 2

Detailed Description

The study comprises three 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. Patients will be treated with single-agent derazantinib or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab. The study enrolls patients with either metastatic or recurrent locally advanced HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction inoperable at the time of screening, and radiologically confirmed disease progression after one or at least one standard treatment regimen.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2 Study of Derazantinib as Monotherapy and Combination Therapy With Paclitaxel, Ramucirumab or Atezolizumab in Patients With HER2-negative Gastric Adenocarcinoma Expressing FGFR2 Genetic Aberrations

Actual Study Start Date :

Oct 6, 2020

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Derazantinib In Substudies 1 and 3.1, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib.	Drug: Derazantinib Derazantinib will be administered orally at a dose of 300 mg once a day and at a dose of 200 mg twice daily as monotherapy in the Substudy 1.
Experimental: Derazantinib-paclitaxel-ramucirumab In Substudies 2 and 3.2, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-paclitaxel-ramucirumab in combination.	Drug: Derazantinib-paclitaxel-ramucirumab Derazantinib will be administered at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 in combination with paclitaxel and ramucirumab. Paclitaxel will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 on days 1, 8, and 15 of a 28-day cycle in combination with derazantinib and ramucirumab. Ramucirumab will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 every 2 weeks in combination with derazantinib and paclitaxel.
Experimental: Derazantinib-atezolizumab In Substudy 3.3, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-atezolizumab in combination.	Drug: Derazantinib-atezolizumab Derazantinib will be administered orally at a dose of 300 mg once a day in combination with atezolizumab. Atezolizumab will be administered intravenously at a dose of 1200 mg every 3 weeks in combination with derazantinib.
Active Comparator: Standard of care In Substudy 3.4, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive the Standard of Care drugs paclitaxel-ramucirumab in combination.	Drug: Paclitaxel-ramucirumab Paclitaxel will be 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 will be administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel.

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) per RECIST 1.1 in Substudy 1 (in two subgroups Cohort 1.1 and 1.2) and Substudy 3) [Approximately 30 months]
ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
4-month progression-free survival rate (PFS4, in a subgroup (Cohort 1.3) within Substudy 1) [Approximately 18 months]
PFS4 will be measured by the proportion of patients alive and free of disease progression by blinded independent central review (BICR) per RECIST. 1.1
Recommended phase 2 dose (RP2D) of derazantinib-paclitaxel-ramucirumab in combination (Substudy 2) [Approximately 18 months]
RP2D will be 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 combination.

Secondary Outcome Measures

ORR per RECIST 1.1 in subgroup Cohort 1.3 within Substudy 1and in Substudy 3 [Approximately 24 months]
ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
Disease Control Rate (DCR) [Approximately 24 months]
Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR
Duration of Response (DOR) [Approximately 24 months]
DOR will be calculated from the first date of documented tumor response to disease progression by BICR (or death if no documentation of PD is obtained)
Progression-free Survival (PFS) [Approximately 24 months]
PFS will be measured from patient enrollment to progressive disease (PD) date by BICR
Overall Survival (OS) [Approximately 24 months]
OS will be measured from patient enrollment to time of death
Pharmacokinetic (PK) profile: Peak Plasma Concentration (Cmax) of derazantinib 200 mg twice daily monotherapy [Approximately 24 months]
Derazantinib plasma concentrations including Cmax will be assessed by measurements in plasma samples
Pharmacokinetic (PK) profile: Area under the plasma concentration versus time curve (AUC) of derazantinib 200 mg twice daily monotherapy [Approximately 24 months]
AUC will be assessed by measurements of derazantinib in plasma samples
Pharmacokinetic (PK) profile: The time to reach Cmax (Tmax) of derazantinib 200 mg twice daily monotherapy [Approximately 24 months]
Tmax will be assessed by measurements of derazantinib in plasma samples

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach
Male or female aged ≥ 18 years
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 disease progression after either standard first- or second-line treatment (Substudy 1), or after standard first-line treatment (Substudies 2 and 3)
Positive test for eligible FGFR aberrations (FGFR2 fusions / rearrangements / amplifications; FGFR1, FGFR2, or FGFR3 mutations / short variants)
Measurable disease as defined by the Investigator using RECIST 1.1 criteria
ECOG PS of 0 or 1
Men and women of childbearing potential must agree to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at least 150 days after the last dose of either investigational drug

Key Exclusion Criteria:

Prior anticancer or investigational drug treatment within an interval shorter than the following, as applicable:

One chemotherapy or biological (e.g., antibody) cycle interval
Five half-lives of any small molecule investigational or licensed medicinal product
Two weeks, for any investigational medicinal product with an unknown half-life
Four weeks of curative radiotherapy
Seven days of palliative radiotherapy

Prior treatment with FGFR Inhibitors (all substudies), and prior treatment with taxanes within 6 months prior to randomization and/or anti-VEGF(R) therapeutic antibody or pathway-targeting agents (Substudies 2 and 3), and prior treatment with anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) therapeutic antibody or pathway-targeting agents (Substudy 3)
Concurrent evidence of clinically significant corneal or retinal disorder
History of clinically significant cardiac disorders and/or a QT interval corrected by Fridericia's formula (QTcF) > 450 ms for males or > 460 ms for females
Known CNS metastases
Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV; known HIV 1/2 antibodies positive); active or chronic hepatitis B without current antiviral therapy and an HBV DNA ≥ 100 IU/mL virus (HBV); active hepatitis C virus (HCV) co-infection; active tuberculosis (for Substudies 2 and 3)
Child-Pugh B or C liver cirrhosis, or a history of hepatic encephalopathy, hepatorenal syndrome, or clinically-meaningful ascites related to cirrhosis (for Substudies 2 and

Administration of a live, attenuated vaccine within 30 days prior to randomization (for Substudy 3)
Treatment with systemic corticosteroids (except for steroidal replacement therapy) or other systemic immunosuppressive medications within 2 weeks prior to first dose of study drug or anticipated requirement for systemic immunosuppressive medications during the study (for Substudy 3)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AdventHealth Cancer Institute	Orlando	Florida	United States	32806
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo	Ciudad Autonoma Buenos Aires		Argentina	B1264AAA
4	Fundación Favaloro para la Docencia e Investigación Médica	Ciudad Autonoma de Buenos Aires		Argentina	C1093AAS
5	Monash Medical Centre Clayton	Clayton		Australia	3168
6	Peter MacCallum Cancer Centre	Melbourne		Australia	3000
7	The Alfred Hospital	Prahran		Australia	3181
8	UZA	Edegem		Belgium	2650
9	UZ Leuven	Leuven		Belgium	3000
10	AZ Delta	Menen		Belgium	8930
11	Liga Norte-Rio-Grandense Contra o Câncer	Natal	Rio Grande Do Norte	Brazil	59075-740
12	Fundação Doutor Amaral Carvalho	Jaú		Brazil	17210-120
13	Instituto Nacional de Câncer José Alencar Gomes da Silva	Rio De Janeiro		Brazil	20230-230
14	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André		Brazil	09060-870
15	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José Do Rio Preto		Brazil	15090-000
16	CeCim Biocinetic	Santiago	Region Met	Chile	8331143
17	Centro de Estudios Clínicos SAGA	Santiago		Chile	7500000
18	Instituto Clinico Oncologico	Temuco		Chile	4810469
19	Institut Sainte Catherine	Avignon		France	84918
20	CHU Besançon - Hôpital Jean Minjoz	Besancon		France	25030
21	Centre Georges François Leclerc	Dijon		France	21079
22	Hôpital Saint-Louis	Paris		France	75475
23	Hôpital Saint-Antoine	Paris		France	75571
24	Institut Gustave Roussy	Villejuif		France	94805
25	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg	Germany	89081
26	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
27	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden	Sachsen	Germany	01307
28	Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt	Dresden		Germany	01067
29	Krankenhaus Nordwest GmbH	Frankfurt		Germany	60488
30	Uniklinik Mainz	Mainz		Germany	55131
31	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
32	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro		Italy	88100
33	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
34	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
35	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano		Italy	20162
36	IOV - Istituto Oncologico Veneto IRCCS	Padova		Italy	35128
37	Istituto Clinico Humanitas	Rozzano		Italy	20089
38	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena		Italy	53100
39	National Cancer Center	Goyang-si		Korea, Republic of	10408
40	Chonnam National University Hwasun Hospital	Hwasun		Korea, Republic of	58128
41	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of	13620
42	Seoul National University Hospital	Seoul		Korea, Republic of	03080
43	Asan Medical Center	Seoul		Korea, Republic of	05505
44	Samsung Medical Center	Seoul		Korea, Republic of	06351
45	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
46	Ajou University Hospital	Suwon		Korea, Republic of	16499
47	Examen sp. z o.o.	Skórzewo		Poland	60-185
48	Centrum Zdrowia MDM	Warszawa		Poland	01-401
49	Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy	Warszawa		Poland	02-781
50	Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna	Łódź		Poland	90-242
51	SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan	Kazan		Russian Federation	420029
52	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow		Russian Federation	115478
53	"VitaMed" LLC	Moscow		Russian Federation	121309
54	BHI of Omsk region "Clinical Oncology Dispensary"	Omsk		Russian Federation	644013
55	FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"	Pesochnyy		Russian Federation	197758
56	Pavlov First Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
57	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	Saint Petersburg		Russian Federation	197758
58	Tomsk Research Instutite of Oncology	Tomsk		Russian Federation	634045
59	SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan	Ufa		Russian Federation	450054
60	Hospital del Mar	Barcelona		Spain	08003
61	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
62	Hospital Clinic de Barcelona	Barcelona		Spain	08036
63	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat		Spain	08908
64	MD Anderson Cancer Centre	Madrid		Spain	28033
65	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
66	Centro Integral Oncologico Clara Campal	Madrid		Spain	28050
67	Clinica Universidad de Navarra	Pamplona		Spain	31008
68	Baskent University Adana Application and Research Center	Adana		Turkey	01220
69	Hacettepe University Medical Faculty	Ankara		Turkey	06100
70	Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital	Ankara		Turkey	06105
71	Ankara City Hospital	Ankara		Turkey	06800
72	Akdeniz University Medical Faculty	Antalya		Turkey	07058
73	Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
74	Istanbul Medeniyet Uni Goztepe Training&Res Hosp	Istanbul		Turkey	34854
75	Kocaeli Universitesi Tip Fakultesi	Kocaeli		Turkey	41380
76	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
77	Ninewells Hospital	Dundee		United Kingdom	DD1 9SY
78	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 OYN
79	University College London Hospitals	London		United Kingdom	W1T7HA
80	The Christie	Manchester		United Kingdom	M20 4BX
81	Royal Marsden Hospital- Sutton	Sutton		United Kingdom	SM2 5PT