FORTITUDE-301: A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression

Sponsor

Amgen (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05325866

Collaborator

(none)

375

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary objectives of this study are to observe the safety and tolerability of bemarituzumab and to evaluate preliminary antitumor activity.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Bemarituzumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

375 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors With FGFR2b Overexpression (FORTITUDE-301)

Anticipated Study Start Date :

Aug 26, 2022

Anticipated Primary Completion Date :

Dec 3, 2024

Anticipated Study Completion Date :

Sep 25, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Monotherapy Dose Exploration Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose.	Drug: Bemarituzumab Intravenous (IV) infusion. Other Names: AMG 552
Experimental: Part 2: Monotherapy Dose Expansion Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1.	Drug: Bemarituzumab Intravenous (IV) infusion. Other Names: AMG 552

Arm

Intervention/Treatment

Experimental: Part 1: Monotherapy Dose Exploration

Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose.

Drug: Bemarituzumab

Intravenous (IV) infusion.

Other Names:

AMG 552

Experimental: Part 2: Monotherapy Dose Expansion

Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1.

Drug: Bemarituzumab

Intravenous (IV) infusion.

Other Names:

AMG 552

Outcome Measures

Primary Outcome Measures

Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [Day 1 to Day 28]
Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [Day 1 to 28 days after last dose (a maximum of 2 years)]
Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs.
Part 1: Number of Participants Who Experience a Treatment-related Adverse Event [Day 1 to 28 days after last dose (a maximum of 2 years)]
Part 2: Objective Response (OR) Rate [Up to approximately 2 years]
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 (RECIST v1.1).

Secondary Outcome Measures

Part 1: OR Rate [Up to approximately 2 years]
OR = CR + PR, measured by CT or MRI as determined by investigator per RECIST v1.1.
Parts 1 and 2: Disease Control (DC) Rate [Up to approximately 2 years]
DC = CR, PR, or stable disease (SD).
Parts 1 and 2: Duration of Response (DOR) [Up to approximately 2 years]
DOR, defined as the time from first documentation of OR (as determined by investigator per RECIST v1.1) until the first documentation of disease progression or death due to any cause, whichever occurs first. Only participants who have achieved OR will be evaluated for DOR. DOR will be censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy.
Parts 1 and 2: Time to Response [Up to approximately 2 years]
Parts 1 and 2: Progression-free Survival (PFS) [Up to approximately 2 years]
PFS, defined as time from first dose of investigational product until the first documentation of radiologic disease progression or death due to any cause. PFS will be censored at the last evaluable post-baseline tumor assessment prior to subsequent therapy. Progression will be based on RECIST v1.1 (derived utilizing investigator tumor assessments).
Parts 1 and 2: Overall Survival (OS) [Up to approximately 2 years]
OS, defined as time from first dose of investigational product until death from any cause. Participants still alive will be censored at the date last known to be alive.
Part 2: Number of Participants Who Experience a TEAE [Day 1 to 28 days after last dose (a maximum of 2 years)]
AEs are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs.
Part 2: Number of Participants Who Experience a Treatment-related AE [Day 1 to 28 days after last dose (a maximum of 2 years)]
Parts 1 and 2: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [Day 1 to 28 days after last dose (a maximum of 2 years)]
Parts 1 and 2: Maximum Observed Serum Concentration (Cmax) of Bemarituzumab [Day 1 to 28 days after last dose (a maximum of 2 years)]
Parts 1 and 2: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [Day 1 to 28 days after last dose (a maximum of 2 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years (or legal adult age within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed
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 exist for the participant, or the participant cannot tolerate or refuses standard of care anticancer therapy, the participant may be allowed to participate on the study after discussion between the investigator and Amgen medical monitor. Participants 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
esophageal squamous cell carcinoma: ≥ 1 line of therapy
triple-negative breast cancer: ≥ 2 lines of therapy
pancreatic ductal adenocarcinoma: ≥ 1 line of therapy
Intrahepatic cholangiocarcinoma ≥ 1 line of therapy
colorectal adenocarcinoma: ≥ 2 lines of therapy
platinum resistant ovarian epithelial cell carcinoma, 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

Disease that is unresectable, locally advanced, or metastatic (not amenable to curative therapy)
Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing
Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ function as determined per protocol.

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 carcinoma, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma
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
History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
Unwillingness to avoid use of contact lenses during study treatment and for at least 100 days after the end of treatment
Recent (within 6 months) corneal surgery or ophthalmic laser treatment or recent (within 6 months) history of, or evidence of, corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer prior/concomitant therapy
Prior treatment with any investigational selective inhibitor of the fibroblast growth factor (FGF)/FGF receptor pathway (unless approved standard of care for tumor indication).