E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression |
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E.1.1.1 | Medical condition in easily understood language |
Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084227 |
E.1.2 | Term | Gastroesophageal junction cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 mFOLFOX6 and nivolumab to placebo plus mFOLFOX6 and nivolumab asassessed by overall survival |
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E.2.2 | Secondary objectives of the trial |
Phase 1b – Safety Lead-In •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) -Objective response (OR) •To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 and nivolumab compared to placbo plus mFOLFOX6 and nivolumab •To compare efficacy between the treatment arms as assessed by: -Duration of response (DOR) -Disease control •To assess subject-reported and quality of life (QoL) outcomes •To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with mFOLFOX6 and nivolumab •To characterize the immunogenicity of bemarituzumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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); with the exception of participants with Gilbert's disease) Calculated or measured creatinine clearance (CrCl) of ≥ 50 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.
Additional Inclusion Criteria Part 2: - No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab. Prior adjuvant or neo-adjuvant therapy for localized disease is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment. - Fibroblast growth factor receptor 2b (FGFR2b) overexpression as determined by centrally performed immunohistochemistry (IHC) testing
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E.4 | Principal 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 - Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer - 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
Please refer to protocol for remaining exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1b – Safety Lead-In •Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, electrocardiogram (ECG), physical examinations, and clinical laboratory tests
Phase 3 •Overall survival, defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety: throughout Phase 1b of the study OS: every 3 months (± 1 month) after the safety follow-up visit until 443 total deaths have been observed in the study or 15 months after the last subject is enrolled (whichever occurs later) |
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E.5.2 | 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 •Objective response •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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS, ORR, DOR: Radiological/tumor assessment: Every 8 weeks until week 56 after cycle 1 day 1, then every 12 weeks; 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)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
to assess Tolerability, Immunogenicity, Biomarkers and Patient-reported Outcomes
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 146 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Taiwan |
Thailand |
United States |
Austria |
France |
Poland |
Romania |
Spain |
Switzerland |
Czechia |
Germany |
Italy |
Belgium |
Hungary |
Portugal |
Russian Federation |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, long-term follow-up, additional antibody testing), as applicable. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |