A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201) (FORTITUDE-201)

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Bemarituzumab Monotherapy and Combination With Other Anti-Cancer Therapy in Subjects With Squamous-Cell Non-Small-Cell Lung Cancer (FORTITUDE-201)

The primary objectives of this study are to evaluate the safety and tolerability of bemarituzumab monotherapy and combination with other anti-cancer therapies, and to determine the recommended phase 3 dose of bemarituzumab in combination with other anti-cancer therapies.

Study Overview

• Status: Active, not recruiting
• Conditions: Squamous-Cell Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Bemarituzumab; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis - Campus Virga Jesse
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bron Cedex, France, 69677
    • CHU de Lyon - Hopital Louis Pradel
  • Paris Cedex 20, France, 75020
    • Hopital Tenon
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
  • Rennes, France, 35033
    • Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
• Korea, Republic of
  • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
• Poland
  • Konin, Poland, 62-500
    • Przychodnia Lekarska Komed Roman Karaszewski
  • Krakow, Poland, 30-727
    • Pratia MCM Krakow
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne Sp zoo
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
  • Lublin, Poland, 20-609
    • Instytut Genetyki i Immunologii GENIM Spzoo
  • Lublin, Poland, 20-701
    • Centrum Medyczne Hope Clinic Sebastian Szklener
  • Otwock, Poland, 05-400
    • Mazowieckie centrum leczenia
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Andalucía
    • Malaga, Andalucía, Spain, 29011
      • Hospital Regional Universitario de Malaga
    • Sevilla, Andalucía, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Hospital Universitari Vall d Hebron
    • Barcelona, Cataluña, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona
    • Hospitalet de Llobregat, Cataluña, Spain, 08908
      • Institut Catala d Oncologia Hospitalet. Hospital Duran i Reynals
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Complexo Hospitalario Universitario A Coruña Hospital Teresa Herrera
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Einstein Center for Cancer Care
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15211
      • University of Pittsburgh, Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
• Age ≥ 18 years old (or legal adult within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed
• Pathologically confirmed squamous cell lung carcinoma
• Disease that is unresectable, locally advanced or metastatic (not amenable to curative therapy)
• Participants must have archived tumor tissue sample (formalin fixed, paraffin embedded [FFPE] sample [FFPE of excisional, or core needle]) taken within last 5 years or be willing to undergo pre-treatment tumor biopsy (excisional, or core needle) for tissue prior to enrollment
• Participant must have progressed on, or recurred after at least 1 prior systemic therapy (Part 1 and 2 only) or at least 2 prior systemic therapies (Part 3 only) for locally advanced and unresectable or metastatic disease. Prior treatment must include a platinum-based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic disease, either given as one line of therapy or as individual lines of therapy, unless the participant has a medical contraindication to one of the required therapies (which must be documented in the electronic case report form [eCRF]). Additionally, if the participant's tumor was previously identified as having a driver mutation (according to local standard of care or guidelines, e.g., Kirsten rat sarcoma [KRAS] G12C, neurotrophic tyrosine receptor kinase [NTRK]), which has an approved therapy for which the participant is eligible and available, the participant must have received the approved therapy in a prior line of treatment.
• For Part 4, participants may not have received prior systemic therapy for their locally advanced and unresectable or metastatic disease. For Part 4, participants who received peri-operative systemic therapy are eligible if that adjuvant/neoadjuvant therapy was completed at least 12 months prior to diagnosis of locally advanced and unresectable or metastatic disease.
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function as determined per protocol
• Part 2, 3 and 4 only: FGFR2b overexpression as determined by centrally performed immunohistochemistry (IHC) testing

Exclusion Criteria:

• Mixed small-cell lung cancer or mixed non-small cell lung cancer (NSCLC) histology
• Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly
• 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 mm Hg despite optimal treatment (measured following European Society for Hypertension/European Society of Cardiology [ESH/ESC] 2013 guidelines; Section 11.11), uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease, Fridericia's correction formula (QTc) ≥ 470
• Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
• 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
• Part 1 and Part 2: participants that experienced toxicity or hypersensitivity requiring discontinuation of prior docetaxel treatment
• Part 1 only: participants that had disease progression on prior therapy with docetaxel
• Part 2 only: participants have received prior docetaxel in unresectable or metastatic setting (including participants who received prior docetaxel in first line for metastatic disease, but not including participants who received prior docetaxel neoadjuvantly or adjuvantly and did not progress within 6 months of end of therapy)
• Prior treatment with any selective inhibitor of the fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) pathway

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Combination Dose Exploration; Participants with SqNSCLC will receive escalating doses of bemarituzumab in combination with docetaxel.	Drug: Docetaxel; IV infusion; Drug: Bemarituzumab; Intravenous (IV) infusion; Other Names: AMG 552
Experimental: Part 2: Combination Dose Expansion; Participants with SqNSCLC and FGFR2b overexpression will receive the dose of bemarituzumab in combination with docetaxel identified as safe during Part 1.	Drug: Docetaxel; IV infusion; Drug: Bemarituzumab; Intravenous (IV) infusion; Other Names: AMG 552
Experimental: Part 3: Bemarituzumab Monotherapy; Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.	Drug: Bemarituzumab; Intravenous (IV) infusion; Other Names: AMG 552
Experimental: Part 4: Combination Immuno-chemotherapy; Participants with FGFR2b overexpression will receive the dose of bemarituzumab identified as safe during Part 1 in combination with pembrolizumab, carboplatin and either paclitaxel or nab-paclitaxel.	Drug: Paclitaxel; IV infusion; Drug: Nab-paclitaxel; IV infusion; Drug: Carboplatin; IV infusion; Drug: Bemarituzumab; Intravenous (IV) infusion; Other Names: AMG 552; Drug: Pembrolizumab; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 4: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)		Cycle 1 Day 1 to Cycle 1 Day 21 (cycle is 21 days)
Parts 1, 2, 3 and 4: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)	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, physical examinations, clinical laboratory tests, and visual acuity that occur after study treatment administration will be recorded as TEAEs.	Cycle 1 Day 1 to 28 days after last dose (approximately 5 months; cycle is 21 days in Parts 1 and 2, cycle is 14 days in Part 3)

Secondary Outcome Measures

Outcome Measure	Time Frame
Parts 1, 2, 3 and 4: Area Under the Concentration Time Curve (AUC) of Bemarituzumab	Part 1/2/4: Day 1 cycles 1-3, Day 1 every odd numbered cycle thereafter, and 28 days after last dose (cycle=21 days). Part 3: Day 1 and 8 cycle 1, Day 1 cycles 2-3, Day 1 of every odd numbered cycle thereafter, and 28 days after last dose (cycle=14 days)
Parts 1, 2, 3 and 4: Maximum Observed Concentration (Cmax) of Bemarituzumab	Part 1/2/4: Day 1 cycles 1-3, Day 1 every odd numbered cycle thereafter, and 28 days after last dose (cycle=21 days). Part 3: Day 1 and 8 cycle 1, Day 1 cycles 2-3, Day 1 of every odd numbered cycle thereafter, and 28 days after last dose (cycle=14 days)
Parts 1, 2, 3 and 4: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab	Part 1/2/4: Day 1 cycles 1-3, Day 1 every odd numbered cycle thereafter, and 28 days after last dose (cycle=21 days). Part 3: Day 1 and 8 cycle 1, Day 1 cycles 2-3, Day 1 of every odd numbered cycle thereafter, and 28 days after last dose (cycle=14 days)
Parts 1, 2, 3 and 4: Objective Response Rate	Up to approximately 2 years
Parts 1, 2, 3 and 4: Duration of Response	Up to approximately 2 years
Parts 1, 2, 3 and 4: Disease Control Rate	Up to approximately 2 years
Parts 1, 2, 3 and 4: Progression Free Survival	Up to approximately 2 years
Parts 1, 2, 3 and 4: Overall Survival	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Docetaxel; Bemarituzumab; Squamous-Cell Non-Small-Cell Lung Cancer; FGFR2b-positive Squamous-Cell Non-Small-Cell Lung Cancer; SqNSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Docetaxel; Carboplatin; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel; Bemarituzumab
• Other Study ID Numbers: 20210102; 2021-004058-47 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No