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

• ClinicalTrials.gov Identifier: NCT05325866
• Recruitment Status: Recruiting
• First Posted: April 13, 2022
• Last Update Posted: May 9, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: April 6, 2022
• First Posted Date: April 13, 2022
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: September 23, 2022
• Estimated Primary Completion Date: September 8, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2022)

• Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 28 ]
• Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: 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 [ Time Frame: Day 1 to 28 days after last dose (a maximum of 2 years) ]
• Part 2: Objective Response (OR) Rate [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 6, 2022)

• Part 1: OR Rate [ Time Frame: 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 [ Time Frame: Up to approximately 2 years ]
  DC = CR, PR, or stable disease (SD).
• Parts 1 and 2: Duration of Response (DOR) [ Time Frame: 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 [ Time Frame: Up to approximately 2 years ]
• Parts 1 and 2: Progression-free Survival (PFS) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 1 to 28 days after last dose (a maximum of 2 years) ]
• Parts 1 and 2: Maximum Observed Serum Concentration (Cmax) of Bemarituzumab [ Time Frame: 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 [ Time Frame: Day 1 to 28 days after last dose (a maximum of 2 years) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
• 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)
• Brief Summary: The primary objectives of this study are to observe the safety and tolerability of bemarituzumab and to evaluate preliminary antitumor activity.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

Drug: Bemarituzumab

Intravenous (IV) infusion.

Other Name: AMG 552

Study Arms

• 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.
  Intervention: Drug: Bemarituzumab
• 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.
  Intervention: Drug: Bemarituzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2022): 303
• Original Estimated Enrollment (submitted: April 6, 2022): 375
• Estimated Study Completion Date: June 30, 2027
• Estimated Primary Completion Date: September 8, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 18 years (or legal adult age within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed

2. 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
   • 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
   • platinum resistant ovarian epithelial cell 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
3. Disease that is unresectable, locally advanced, or metastatic (not amenable to curative therapy)
4. Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing
5. Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate organ function as determined per protocol.

Exclusion Criteria:

1. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
2. Other solid tumor cohort excludes primary tumors of the CNS, squamous non-small cell lung cancer, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma
3. 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
4. History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
5. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
6. Unwillingness to avoid use of contact lenses during study treatment and for at least 100 days after the end of treatment
7. 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
8. Prior treatment with any investigational selective inhibitor of the fibroblast growth factor (FGF)/FGF receptor pathway (unless approved standard of care for tumor indication).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Finland, France, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT05325866
• Other Study ID Numbers: 20210104
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2 ) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: May 2024