Study plan for the VENTANA FGFR2b (FPR2-D) RxDx test in the Amgen study 20210098.

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Romania, Russian Federation, Singapore, Spain, Switzerland, T?rkiye, Taiwan, Thailand, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
EUCTR2021-003477-61 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
Diagnostic Protocol for VENTANA FGFR2b (FPR2-D) RxDx Assay in Amgen Study 20210098 (BASEC)

Wissenschaftlicher Titel
A Phase 1b/3 Study of Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab Alone in Subjects With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer With FGFR2b Overexpression (FORTITUDE-102) (ICTRP)

Öffentlicher Titel
Bemarituzumab plus Chemotherapy and Nivolumab versus Chemotherapy and Nivolumab Alone (ICTRP)

Untersuchte Krankheit(en)
Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression
MedDRA version: 21.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 23.1Level: LLTClassification code 10084227Term: Gastroesophageal junction cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Untersuchte Intervention

Product Name: Bemarituzumab
Product Code: AMG 552
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BEMARITUZUMAB
Current Sponsor code: AMG 552
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

(ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

Inclusion criteria:
Inclusion Criteria Part 1:
- Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
- Participant must be a candidate to receive mFOLFOX6 and nivolumab
- Adequate organ function as follows:
Absolute neutrophil count = 1.5 x 10^9/L
Platelet count = 100 x 10^9/L
Hemoglobin = 9 g/dl /dL without red blood cell (RBC) transfusion within 7 days prior to the first dose of study treatment
Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) <3 x upper limit of normal (ULN) (or < 5 x ULN if liver involvement). Total bilirubin <1.5 x ULN (or < 2 x ULN if liver involvement); or Gilbert's disease)
Part 1 only: Calculated or measured creatinine clearance (CrCl) of = 50 mL/minute calculated using the formula of Cockcroft and Gault
Part 2 only: Calculated or measured creatinine clearance (CrCl) of = 30 mL/minute calculated using the formula of Cockcroft and Gault International Normalized Ratio (INR) or prothrombin time (PT) < 1.5 ? ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment.
Subject has no contraindications to nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Subjects in Part 1 must have no contraindications to mFOLFOX6. Subjects in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Subjects in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist.
Additional Inclusion Criteria Part 2:
- No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of chemotherapy with or without nivolumab. Prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment.
- Confirmed FGFR2b = 10% 2+/3+ TC by centrally performed immunohistochemistry (IHC) testing based on tumor sample either archival (obtained within 6 months/180 days prior to signing prescreening informed consent) or a fresh biopsy.
- For subjects receiving CAPOX only, the ability to take oral medication.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 406
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 122
(ICTRP)

Exclusion criteria:
- Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
- Known positive human epidermal growth factor receptor 2 (HER2) status
- Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
- Peripheral sensory neuropathy grade 2 or higher
- Clinically significant cardiac disease
- Other malignancy within the last 2 years (exceptions for definitively treated disease)
- Chronic or systemic ophthalmologic disorders
- Major surgery or other investigational study within 28 days prior to randomization
- Palliative radiotherapy within 14 days prior to randomization
-Evidence of, or recent (within 6 months) history of, corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an
increased risk of developing a corneal ulcer. Recent (within 6 months) corneal surgery or ophthalmic laser treatment
- Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study
- For subjects receiving CAPOX only, GI tract disease causing the inability to take oral medication, malabsorption syndrome, or requirement for IV alimentation, or uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis)
Please refer to protocol for remaining exclusion criteria.


Primäre und sekundäre Endpunkte
Main Objective: Phase 1b ? Safety Lead-In
?To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 and nivolumab

Phase 3
?To compare efficacy of bemarituzumab plus chemotherapy and nivolumab to placebo plus chemotherapy and nivolumab asassessed by overall survival in subjects with FGFR2b> 10% 2+/3+ tumor cell staining (FGFR2b>10% 2+/3+ TC);Secondary Objective: Phase 1b
?To evaluate preliminary anti-tumor activity of bemarituzumab plus mFOLFOX6 and nivolumab
?To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with mFOLFOX6 and nivolumab
?To characterize the immunogenicity of bemarituzumab

Phase 3
? To compare efficacy between the treatment arms as assessed by progression-free survival (PFS) and objective response (OR)
? To compare efficacy between treatment arms in all randomized subjects as assessed by: - OS, - PFS, - OR
? To evaluate the safety and tolerability of each treatment arm
? To compare efficacy between treatment arms n FGFR2b> 10% 2+/3+ TC subjects as assessed by:
- duration of response, - disease control
? To assess subject-reported and QoL outcomes in FGFR2b = 10% 2+/3+ TC subjects
? To characterize the PK profile of bemarituzumab when administered with chemotherapy and nivolumab
? To characterize the immunogenicity of bemarituzumab
;Primary end point(s): Phase 1b
?Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, physical examinations, and clinical laboratory tests

Phase 3
? OS, defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive;Timepoint(s) of evaluation of this end point: Safety: throughout Phase 1b of the study
OS: every 12 weeks (? 2 weeks) after safety follow-up visit until 274 deaths in FGFR2b = 10% 2+/3+ TC subjects are reported in the clinical trial database or 15 months after the last subject is enrolled, whichever occurs later. (ICTRP)

Secondary end point(s): Phase 1b ? Safety Lead-In
?Objective response
?Duration of response
?Disease control (DCR)
?Progression free survival (PFS)
?Overall survival (OS)
?PK parameters for bemarituzumab
?Anti-bemarituzumab antibody formation

Phase 3
?PFS
?OR
?OS in all randomized subjects
?PFS in all randomized subjects
?ORR in all randomized subjects
?Treatment-emergent adverse events (including all adverse events, grade = 3, serious adverse events, fatal adverse events, and adverse events requiring permanent discontinuation of investigational product)
?Clinically significant changes in vital signs, visual acuity, and clinical laboratory tests
?Duration of response
?Disease control
?Subjective score and change from baseline in following assessments:
- EORTC Quality of Life Questionnaire Version 3.0(QLQ-C30) individual scores (raw and transformed) for the 5 functional scales, 9 symptom scales, global health status/quality of life scale and change from baseline at each assessment
- Stomach cancer related symptoms measured by EORTC-QLQ-STO22
- Summary scores at each assessment and changes from baseline of visual analogue scale (VAS) scores as measured by EuroQol 5- dimensional (EQ-5D-5L)
- Time to deterioration in stomach-cancer related symptoms scores
- Time to deterioration in health-related quality of life (HRQoL) scores
- Time to deterioration in physical function scores
?PK parameters for bemarituzumab
?Anti-bemarituzumab antibody formation;Timepoint(s) of evaluation of this end point: PFS, ORR, DOR: Radiological/tumor assessment: Every 6 weeks (? 7 days) from cycle 1 day 1 until week 54 , then every 12 weeks (? 14 days);
until start of new anticancer therapy, disease progression, death, withdrawal of consent, or end of study, whichever occurs first.
TAEs: throughout study

For other endpoints see Schedule of Activity (SoA)
(ICTRP)

Registrierungsdatum
16.10.2024 (ICTRP)

Einschluss des ersten Teilnehmers
25.01.2023 (ICTRP)

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Departamentul Medical, medinfo-romania@amgen.com, 0040215273000, Amgen Romania SRL (ICTRP)

Sekundäre IDs
20210098, NCT05111626, 2023-505458-16, 2021-003477-61-DE (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003477-61 (ICTRP)