A Study Evaluating Bemarituzumab in Solid Tumors with FGFR2b Overexpression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jun 2022 → 29 Jan 2026

Decision date (initial)

2024-09-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-505455-44-00

EudraCT number

2021-006386-38

WHO UTN

U1111-1292-8521

ClinicalTrials.gov

NCT05325866

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy, Pharmacokinetic, Others

Phase 1b: To observe the safety and tolerability of bemarituzumab
Phase 2: To evaluate preliminary antitumor activity

Secondary objectives 5

1. Phase 1b: To evaluate preliminary antitumor activity
2. Phase 1b: Characterize the pharmacokinetics (PK) of bemarituzumab
3. Phase 2: To evaluate other measures of preliminary antitumor activity
4. Phase 2: To evaluate the safety and tolerability of bemarituzumab
5. Phase 2: Characterize the PK of bemarituzumab monotherapy

Conditions and MedDRA coding

Solid tumours

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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, as specified below. If no standard of care therapies exists for the subject, or the subject cannot tolerate or refuses standard of care anticancer therapy, the subject may be allowed to participate on the study after discussion between the investigator and Amgen medical monitor. Subjects who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving bemarituzumab are available prior to consenting to participate in the trial. head and neck squamous cell carcinoma: ≥ 1 line of therapy triple-negative breast cancer: ≥ 2 lines of therapy intrahepatic cholangiocarcinoma: ≥ 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: ≥ 1 line of therapy endometrial adenocarcinoma: ≥ 1 line of therapy cervical carcinoma: ≥ 1 line of therapy other solid tumors: ≥ 1 line of therapy
2. Tumor overexpresses FGFR2b as determined by centrally performed IHC testing
3. Measurable disease per RECIST v1.1
4. Adequate hematologic and organ function, defined as follows: Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL AST and ALT < 3 x upper limit of Normal [ULN] (or < 5 x ULN in case of liver involvement). Total bilirubin < 1.5 x ULN (or < 2 x ULN in case of liver involvement or Gilbert’s disease) Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault ([140 – Age] x Mass[kg]/[72 x Creatinine mg/dL) (x 0.85 if female). International normalized ratio (INR) or prothrombin time (PT) < 1.5 × ULN except for subjects receiving anticoagulation therapy, who must be on stable dose of anticoagulant therapy for 6 weeks prior to enrollment.

Exclusion criteria 11

1. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease Subjects with asymptomatic CNS metastases are eligible if clinically stable for at least 4 weeks and do not require intervention (including use of corticosteroids). Subjects with treated brain metastases are eligible provided the following criteria are met: Definitive therapy was completed at least 2 weeks prior to the first planned dose of study treatment (stereotactic radiosurgery at least 7 days prior to first planned dose of study treatment). At least 7 days prior to first planned dose of study treatment: any CNS disease is clinically stable, subject is off steroids for CNS disease (unless steroids are indicated for a reason unrelated to CNS disease), and subject is off or on stable doses of anti-epileptic drugs.
2. Other solid tumor cohort excludes primary tumors of the CNS, squamous non-small cell lung cancer, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma
3. History of other malignancy within the past 2 years, with the following exceptions: curatively treated non-melanoma skin malignancy cervical cancer in situ curatively treated uterine cancer stage I curatively treated ductal or lobular breast carcinoma in situ and not currently receiving any systemic therapy localized prostate cancer that has been treated surgically with curative intent and presumed cured
4. Impaired cardiac function or clinically significant cardiac disease including: unstable angina within 6 months prior to first dose of study treatment, acute myocardial infarction < 6 months prior to first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure > 160 mmHg or diastolic >100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval (QTc) ≥ 470.
5. Active infection requiring systemic treatment or any uncontrolled infection within 14 days prior to first dose of study treatment
6. Known human immunodeficiency virus (HIV) infection with CD4+ T-cell (CD4+) counts <350 cells/μL, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response following antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen [SAg] or core antibody that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed).
7. History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
8. Prior treatment with any investigational selective inhibitor of the FGF-FGFR pathway (unless approved standard of care for tumor indication)
9. Any anticancer therapy or immunotherapy within 4 weeks prior to enrollment; Palliative radiotherapy is allowed, provided it has been completed more than 14 days prior to the first dose of study treatment All treatment-related toxicity needs to be resolved to grade ≤ 1 prior to the first dose of study treatment, with exception of alopecia or toxicities considered irreversible (defined as having been present and stable > 21 days) which are not otherwise described in the exclusion criteria
10. Major surgical procedure within 28 days prior to first dose of study treatment
11. Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 90 days after the last dose of bemarituzumab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1b: 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
2. Phase 2: Objective response (OR) (OR = complete response [CR] + partial response [PR]), measured by computed tomography (CT) or magnetic resonance imaging (MRI) as determined by investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Secondary endpoints 9

1. Phase 1b: Objective response (OR)
2. Phase 1b and 2: Disease control (DC) (CR, PR, or stable disease [SD])
3. Phase 1b and 2: Time to response (TTR)
4. Phase 1b and 2: Overall survival (OS)
5. Phase 1b: PK parameters for bemarituzumab including, but not limited to, area under the concentration time curve (AUC), maximum observed serum concentration (Cmax), and the observed concentration at the end of a dose interval (Ctrough)
6. Phase 2: PK parameters for bemarituzumab including, but not limited to, AUC, Cmax, and Ctrough
7. Phase 2: Treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, and clinical laboratory tests
8. Phase 1b and 2: Duration of response (DOR)
9. Phase 1b and 2: Progression-free survival (PFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 8

Locations

15 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 157 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications