E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors with FGFR2b Overexpression |
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E.1.1.1 | Medical condition in easily understood language |
A Study Evaluating Bemarituzumab in Solid Tumors 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 | 26.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast 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 | 27.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073077 |
E.1.2 | Term | Intrahepatic cholangiocarcinoma |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033131 |
E.1.2 | Term | Ovarian carcinoma |
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 | 27.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014720 |
E.1.2 | Term | Endometrial adenocarcinoma |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008239 |
E.1.2 | Term | Cervical carcinoma recurrent |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001160 |
E.1.2 | Term | Adenocarcinoma lung |
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: •To observe the safety and tolerability of bemarituzumab Phase 2: •To evaluate preliminary antitumor activity |
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E.2.2 | Secondary objectives of the trial |
Phase 1b: •To evaluate other measures of preliminary antitumor activity •Characterize the PK of bemarituzumab monotherapy Phase 2: •To evaluate other measures of preliminary antitumor activity •To evaluate the safety and tolerability of bemarituzumab •Characterize the PK of bemarituzumab monotherapy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults with histologically or cytologically confirmed cancer of one of the following types, refractory to or relapsed after at least 1 prior standard therapeutic regimen in the advanced/metastatic setting: - head and neck squamous cell carcinoma: more than or equal to 1 line of therapy -triple-negative breast cancer: more than or equal to 2 lines of therapy -intrahepatic cholangiocarcinoma: more than or equal to 1 line of therapy -lung adenocarcinoma: at least platinum-based chemotherapy, checkpoint inhibitor, and targeted therapy (ie, if molecular testing has identified targetable mutations in EGFR, ALK, etc) -platinum-resistant ovarian epithelial carcinoma, including fallopian tube cancers and primary peritoneal cancers, defined as progression during or within 6 months of a platinum containing regimen: more than or equal to 1 line of therapy -endometrial adenocarcinoma: more than or equal to 1 line of therapy -cervical carcinoma: more than or equal to 1 line of therapy -other solid tumors: more than or equal to 1 line of therapy •Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing •Measurable disease per RECIST v1.1 •Adequate hematologic and organ function, defined as follows: -Absolute neutrophil count more than or equal to 1.5 x 109/L -Platelet count more than or equal to 100 x 109/L -Hemoglobin more than or equal to 9 g/dL -AST and ALT less than 3 x upper limit of Normal [ULN] (or < 5 x ULN in case of liver involvement). Total bilirubin less than 1.5 x ULN (or less than 2 x ULN in case of liver involvement OR Gilbert’s disease)
For more details please see section 5.1 Inclusion Criteria within the Protocol |
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E.4 | Principal exclusion criteria |
•Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease •Other solid tumor cohort excludes primary tumors of the CNS, squamous non small cell lung cancer, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma •History of other malignancy within the past 2 years (see exceptions within the Protocol) •Impaired cardiac function or clinically significant cardiac disease •Active infection requiring systemic treatment or any uncontrolled infection within 14 days prior to first dose of study treatment •Known human immunodeficiency virus (HIV) infection •History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids •Prior treatment with any investigational selective inhibitor of the FGF-FGFR pathway (unless approved standard of care for tumor indication) •Any anticancer therapy or immunotherapy within 4 weeks prior to enrollment (see additional details within the Protocol) •Major surgical procedure within 28 days prior to first dose of study treatment. •Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.
For more details please see section 5.2 Exclusion Criteria within the Protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: •Dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, and clinical laboratory tests Phase 2: •Objective Response (OR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoints to be assessed throughout the course of the study. (See Table 1-1 in section 1.3 Schedule of Activities in Protocol) |
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E.5.2 | Secondary end point(s) |
Phase 1 and Phase 2: Objective response (OR) •Disease control (DC) (CR, PR, or stable disease [SD]) •Duration of response (DOR) •Time to response (TTR) •Progression-free survival (PFS) •Overall survival (OS) •PK parameters for bemarituzumab including, but not limited to, AUC, Cmax, and Ctrough •PK parameters for bemarituzumab including, but not limited to, area under the concentration time curve (AUC), maximum observed concentration (Cmax), and the observed concentration at the end of a dose interval (Ctrough)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OR, DC, DOR, TTR, PFS: •Radiographic assessment to be performed every 8 weeks (± 7 days) until week 56 and then every 12 weeks (± 14 days) until radiographic progression or initiation of subsequent anticancer therapy. OS: •To be assessed after subject enrollment and throughout the course of the study. After safety follow-up subjects will undergo long term follow-up for survival approximately every 3 months (± 1 month) for up to 2 years from the first dose of bemarituzumab. (See Table 1-1 in section 1.3 Schedule of Activities in Protocol) |
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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 | Yes |
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 |
Assess tolerability, characterize immunogenicity and biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Switzerland |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
Czechia |
Denmark |
Finland |
France |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Romania |
Spain |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | No |
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, 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |