Clinical trial NCT04604132: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Gastric Adenocarcinoma
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
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
First posted: 2020-10-27
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
timeFrame: From first dose and up to 18 months
measure: Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
timeFrame: From first dose and up to 4 months
measure: Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
timeFrame: From first dose and up to 18 months
Secondary outcomes:
measure: ORR in Substudy 1 in Cohort 1.3
timeFrame: From first dose and up to 9 months
measure: Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts
timeFrame: From first dose and up to 18 months
measure: PFS in Substudy 1 in Cohort 1.3
timeFrame: From first dose and up to 9 months
measure: Overall Survival (OS) in Substudy 1 in Cohort 1.3
timeFrame: From first dose and up to 9 months
measure: OS in Substudy 2
timeFrame: From first dose and up to 15 months
measure: ORR in Substudy 2
timeFrame: From first dose and up to 15 months
measure: DCR in Substudy 2
timeFrame: From first dose and up to 15 months
measure: DOR in Substudy 2 (Separate and Combined Cohorts)
timeFrame: From first dose and up to 15 months
measure: PFS in Substudy 2
timeFrame: From first dose and up to 15 months
measure: Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Fundación Favaloro para la Docencia e Investigación Médica
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Prahran
country: Australia
facility: The Alfred Hospital
city: Edegem
country: Belgium
facility: UZA
city: Leuven
country: Belgium
facility: UZ Leuven
city: Menen
country: Belgium
facility: AZ Delta
city: Natal
country: Brazil
facility: Liga Norte-Rio-Grandense Contra o Câncer
state: Rio Grande Do Norte
city: Jaú
country: Brazil
facility: Fundação Doutor Amaral Carvalho
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Câncer José Alencar Gomes da Silva
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: Santiago
country: Chile
facility: CeCim Biocinetic
state: Region Met
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA
city: Temuco
country: Chile
facility: Instituto Clinico Oncologico
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besancon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
state: Sachsen
city: Dresden
country: Germany
facility: Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Mainz
country: Germany
facility: Uniklinik Mainz
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Skórzewo
country: Poland
facility: Examen sp. z o.o.
city: Warszawa
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Łódź
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
city: Kazan
country: Russian Federation
facility: SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
city: Moscow
country: Russian Federation
facility: "VitaMed" LLC
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Pesochnyy
country: Russian Federation
facility: FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
city: Tomsk
country: Russian Federation
facility: Tomsk Research Instutite of Oncology
city: Ufa
country: Russian Federation
facility: SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Adana
country: Turkey
facility: Baskent University Adana Application and Research Center
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet Uni Goztepe Training&Res Hosp
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital- Sutton
Study officials:
affiliation: Basilea Pharmaceutica International Ltd, Allschwil
name: Manuel Häckl, MD
role: STUDY_DIRECTOR
References: