Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma

NCT04604132 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: DZB-CS-202
• Study Type: interventional
• Target: 47
• Locations: 15 countries
• Sites: 81

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).

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

Outcome Measures

Primary Outcomes (3)

• 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 (10)

• ORR in Substudy 1 in Cohort 1.3

  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

  From first dose and up to 18 months

• PFS in Substudy 1 in Cohort 1.3

  From first dose and up to 9 months

• Overall Survival (OS) in Substudy 1 in Cohort 1.3

  From first dose and up to 9 months

• OS in Substudy 2

  From first dose and up to 15 months

Study Arms (5)

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

Drug: Derazantinib-paclitaxel-ramucirumab combination

Interventions

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

Derazantinib-paclitaxel-ramucirumab combination DRUG

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.

Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (81)

AdventHealth Cancer Institute

Orlando, Florida, 32806, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Fundación Favaloro para la Docencia e Investigación Médica

Buenos Aires, C1093AAS, Argentina

Location

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Ciudad Autonoma Buenos Aires, B1264AAA, Argentina

Location

Monash Medical Centre Clayton

Clayton, 3168, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

The Alfred Hospital

Prahran, 3181, Australia

Location

UZA

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

AZ Delta

Menen, 8930, Belgium

Location

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

Fundação Doutor Amaral Carvalho

Jaú, 17210-120, Brazil

Location

Instituto Nacional de Câncer José Alencar Gomes da Silva

Rio de Janeiro, 20230-230, Brazil

Location

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, 09060-870, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

CeCim Biocinetic

Santiago, Region Met, 8331143, Chile

Location

Centro de Estudios Clínicos SAGA

Santiago, 7500000, Chile

Location

Instituto Clinico Oncologico

Temuco, 4810469, Chile

Location

Institut Sainte Catherine

Avignon, 84918, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Hôpital Saint-Antoine

Paris, 75571, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 01307, Germany

Location

Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt

Dresden, 01067, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, 60488, Germany

Location

Uniklinik Mainz

Mainz, 55131, Germany

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, 88100, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, 20162, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna

Lodz, 90-242, Poland

Location

Examen sp. z o.o.

Skórzewo, 60-185, Poland

Location

Centrum Zdrowia MDM

Warsaw, 01-401, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan

Kazan', 420029, Russia

Location

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, 115478, Russia

Location

"VitaMed" LLC

Moscow, 121309, Russia

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, 644013, Russia

Location

FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"

Pesochnyy, 197758, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, 197758, Russia

Location

Tomsk Research Instutite of Oncology

Tomsk, 634045, Russia

Location

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, 450054, Russia

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

MD Anderson Cancer Centre

Madrid, 28033, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Baskent University Adana Application and Research Center

Adana, 01220, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital

Ankara, 06105, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Akdeniz University Medical Faculty

Antalya, 07058, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Istanbul Medeniyet Uni Goztepe Training&Res Hosp

Istanbul, 34854, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 OYN, United Kingdom

Location

University College London Hospitals

London, W1T7HA, United Kingdom

Location

The Christie

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hospital- Sutton

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Stomach Neoplasms; Acrocephalosyndactylia

Interventions

derazantinib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Manuel Häckl, MD
• Organization: Basilea Pharmaceutica International Ltd, Allschwil

manuel.haeckl@basilea.com

+41 76 302 53 10

Study Officials

• Manuel Häckl, MD

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 27, 2020
• Study Start: October 6, 2020
• Primary Completion: November 21, 2022
• Study Completion: November 21, 2022
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); CL (3); AU (3); FR (6); PL (4); RU (9); IT (8); DE (6); BR (5); KR (8); US (2); ES (8); AR (2); BE (3); TU (8)