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

Sponsor
Basilea Pharmaceutica (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04604132
Collaborator
(none)
254
Enrollment
83
Locations
4
Arms
32.8
Anticipated Duration (Months)
3.1
Patients Per Site
0.1
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).

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
Anticipated Enrollment :
254 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

ArmIntervention/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

  1. 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).

  2. 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

  3. 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

  1. 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).

  2. Disease Control Rate (DCR) [Approximately 24 months]

    Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR

  3. 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)

  4. Progression-free Survival (PFS) [Approximately 24 months]

    PFS will be measured from patient enrollment to progressive disease (PD) date by BICR

  5. Overall Survival (OS) [Approximately 24 months]

    OS will be measured from patient enrollment to time of death

  6. 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

  7. 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

  8. 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:
No
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:
  1. One chemotherapy or biological (e.g., antibody) cycle interval

  2. Five half-lives of any small molecule investigational or licensed medicinal product

  3. Two weeks, for any investigational medicinal product with an unknown half-life

  4. Four weeks of curative radiotherapy

  5. 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

SiteCityStateCountryPostal Code
1Banner MD Anderson Cancer CenterGilbertArizonaUnited States85234
2AdventHealth Cancer InstituteOrlandoFloridaUnited States32806
3Winship Cancer InstituteAtlantaGeorgiaUnited States30322
4Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
5Hospital de Gastroenterologia Dr. Carlos Bonorino UdaondoCiudad Autonoma Buenos AiresArgentinaB1264AAA
6Fundación Favaloro para la Docencia e Investigación MédicaCiudad Autonoma de Buenos AiresArgentinaC1093AAS
7Monash Medical Centre ClaytonClaytonAustralia3168
8Peter MacCallum Cancer CentreMelbourneAustralia3000
9The Alfred HospitalPrahranAustralia3181
10UZAEdegemBelgium2650
11UZ LeuvenLeuvenBelgium3000
12AZ DeltaMenenBelgium8930
13Liga Norte-Rio-Grandense Contra o CâncerNatalRio Grande Do NorteBrazil59075-740
14Fundação Doutor Amaral CarvalhoJaúBrazil17210-120
15Instituto Nacional de Câncer José Alencar Gomes da SilvaRio De JaneiroBrazil20230-230
16CEPHO - Centro de Estudos e Pesquisas de Hematologia e OncologiaSanto AndréBrazil09060-870
17Fundação Faculdade Regional de Medicina de São José do Rio PretoSão José Do Rio PretoBrazil15090-000
18CeCim BiocineticSantiagoRegion MetChile8331143
19Centro de Estudios Clínicos SAGASantiagoChile7500000
20Instituto Clinico OncologicoTemucoChile4810469
21Institut Sainte CatherineAvignonFrance84918
22CHU Besançon - Hôpital Jean MinjozBesanconFrance25030
23Centre Georges François LeclercDijonFrance21079
24Hôpital Saint-LouisParisFrance75475
25Hôpital Saint-AntoineParisFrance75571
26Institut Gustave RoussyVillejuifFrance94805
27Universitaetsklinikum UlmUlmBaden WuerttembergGermany89081
28Medizinische Hochschule HannoverHannoverNiedersachsenGermany30625
29Universitaetsklinikum Carl Gustav Carus TU DresdenDresdenSachsenGermany01307
30Staedtisches Klinikum Dresden Standort Dresden-FriedrichstadtDresdenGermany01067
31Krankenhaus Nordwest GmbHFrankfurtGermany60488
32Uniklinik MainzMainzGermany55131
33Azienda Ospedaliera Universitaria Policlinico Sant'Orsola MalpighiBolognaItaly40138
34Azienda Ospedaliero Universitaria Mater DominiCatanzaroItaly88100
35Fondazione IRCCS Istituto Nazionale dei TumoriMilanoItaly20133
36IEO Istituto Europeo di OncologiaMilanoItaly20141
37Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)MilanoItaly20162
38IOV - Istituto Oncologico Veneto IRCCSPadovaItaly35128
39Istituto Clinico HumanitasRozzanoItaly20089
40A.O.U. Senese Policlinico Santa Maria alle ScotteSienaItaly53100
41National Cancer CenterGoyang-siKorea, Republic of10408
42Chonnam National University Hwasun HospitalHwasunKorea, Republic of58128
43Seoul National University Bundang HospitalSeongnamKorea, Republic of13620
44Seoul National University HospitalSeoulKorea, Republic of03080
45Asan Medical CenterSeoulKorea, Republic of05505
46Samsung Medical CenterSeoulKorea, Republic of06351
47The Catholic University of Korea, Seoul St. Mary's HospitalSeoulKorea, Republic of06591
48Ajou University HospitalSuwonKorea, Republic of16499
49Examen sp. z o.o.SkórzewoPoland60-185
50Centrum Zdrowia MDMWarszawaPoland01-401
51Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut BadawczyWarszawaPoland02-781
52Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjnaŁódźPoland90-242
53SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic TatarstanKazanRussian Federation420029
54FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"MoscowRussian Federation115478
55"VitaMed" LLCMoscowRussian Federation121309
56BHI of Omsk region "Clinical Oncology Dispensary"OmskRussian Federation644013
57FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"PesochnyyRussian Federation197758
58Pavlov First Saint Petersburg State Medical UniversitySaint PetersburgRussian Federation197022
59FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"Saint PetersburgRussian Federation197758
60Tomsk Research Instutite of OncologyTomskRussian Federation634045
61SBIH Republican Clinical Oncological Dispensary of the MoH of Republic BashkortostanUfaRussian Federation450054
62Hospital del MarBarcelonaSpain08003
63Hospital Universitari Vall d'HebronBarcelonaSpain08035
64Hospital Clinic de BarcelonaBarcelonaSpain08036
65ICO l'Hospitalet - Hospital Duran i ReynalsL'Hospitalet de LlobregatSpain08908
66MD Anderson Cancer CentreMadridSpain28033
67Hospital Universitario Ramon y CajalMadridSpain28034
68Centro Integral Oncologico Clara CampalMadridSpain28050
69Clinica Universidad de NavarraPamplonaSpain31008
70Baskent University Adana Application and Research CenterAdanaTurkey01220
71Hacettepe University Medical FacultyAnkaraTurkey06100
72Dr. Abdurrahman Yurtaslan Oncology Teaching and Research HospitalAnkaraTurkey06105
73Ankara City HospitalAnkaraTurkey06800
74Akdeniz University Medical FacultyAntalyaTurkey07058
75Istanbul University Cerrahpasa - Cerrahpasa Medical FacultyIstanbulTurkey34098
76Istanbul Medeniyet Uni Goztepe Training&Res HospIstanbulTurkey34854
77Kocaeli Universitesi Tip FakultesiKocaeliTurkey41380
78Addenbrooke's HospitalCambridgeUnited KingdomCB2 0QQ
79Ninewells HospitalDundeeUnited KingdomDD1 9SY
80Beatson West of Scotland Cancer CentreGlasgowUnited KingdomG12 OYN
81University College London HospitalsLondonUnited KingdomW1T7HA
82The ChristieManchesterUnited KingdomM20 4BX
83Royal Marsden Hospital- SuttonSuttonUnited KingdomSM2 5PT

Sponsors and Collaborators

  • Basilea Pharmaceutica

Investigators

  • Study Director: Inessa Polyakova, MD, Basilea Pharmaceutica International Ltd

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Basilea Pharmaceutica
ClinicalTrials.gov Identifier:
NCT04604132
Other Study ID Numbers:
  • DZB-CS-202
First Posted:
Oct 27, 2020
Last Update Posted:
Mar 8, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Basilea Pharmaceutica
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 8, 2022