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: Terminated
• 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 (Actual): 74
• Phase: Phase 1

Contacts and Locations

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 - Hôpital 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 Ramón 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 Coruna 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
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4	DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and included the below if considered by the investigator to be related to study drug, excluding toxicities related to disease progression or intercurrent illness: Grade 3 thrombocytopenia for > 7 days or with Grade > 2 bleeding, vomiting/diarrhea for > 3 days, fatigue; Grade ≥ 3 febrile neutropenia, nausea for > 3 days; Grade 4 neutropenia, thrombocytopenia, anemia, ophthalmologic AE, laboratory value, vomiting/diarrhea; Grade 5 toxicity (death not due to disease progression). CTCAE Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 results in death.	Day 1 to Day 21 of Cycle 1 (each cycle was 21 days)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a clinical trial participants. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to 28 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered possibly related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment, clinical laboratory tests, and visual acuity were recorded as TEAEs. A serious TEAE resulted in death, was immediately life threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. AEs of special interest (AESIs) were ocular events of any CTCAE grade or seriousness occurring up to 100 days after the last dose of bemarituzumab.	Day 1 of cycle 1 to 100 days after the last dose of study treatment or end of study date, whichever occurred earlier (Parts 1, 2, and 4 cycle length = 21 days; Part 3 cycle length = 14 days). Median treatment duration was 6.2 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab	Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis.	Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose
Maximum Observed Serum Concentration (Cmax) of Bemarituzumab	Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis.	Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose
Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab	Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis.	Pre-dose Cycle 2 Day 1 and Cycle 3 day 1
Percentage of Participants Who Achieved an Objective Response (OR)	OR was defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. All lymph nodes must have been non-pathological in size (< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the long term follow-up (LTFU) period (median time on study was approximately 21 weeks)
Duration of Response (DOR)	DOR was defined as the time from the first documentation of OR (determined by the investigator per RECIST v1.1) until first documentation of disease progression or death due to any cause, whichever occurred first. DOR was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at date of first documentation of OR (i.e., assigned a one-day interval).	Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks)
Disease Control Rate (DCR)	DCR was defined as the percentage of participants documented to have a CR, PR or stable disease (SD) per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. All lymph nodes must have been non-pathological in size (< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions.	Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks)
Progression-free Survival (PFS)	PFS was defined as the time from date of first dose of investigational product until the first documentation of radiologic disease progression or death due to any cause, whichever occurred first, in the absence of subsequent anticancer therapy. PFS was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at first dose of investigational product. Progression was based on RECIST v1.1 criteria. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions.	Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks
Overall Survival (OS)	OS was defined as the time from the date of first dose of investigational product until event of death due to any cause through the analysis cutoff date. Participants still alive were censored at the date last known to be alive through the analysis cutoff date.	Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks

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 (Actual): May 28, 2024
• Study Completion (Actual): May 28, 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): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: February 1, 2025

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: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Albumin-Bound Paclitaxel; Bemarituzumab; Carboplatin; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: 20210102; 2021-004058-47 (EudraCT Number); 2023-505456-22 (Other Identifier: EU CT 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