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FORTITUDE-201: A Study of Bemarituzumab Monotherapy and Docetaxel Combination in Participants With Squamous Non-small-cell Lung Cancer (SqNSCLC) With Fibroblast Growth Factor Receptor Isoform 2b (FGFR2b) Overexpression

Sponsor
Amgen (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05267470
Collaborator
(none)
108
Enrollment
25
Locations
3
Arms
39.4
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the safety and tolerability of bemarituzumab monotherapy and in combination with docetaxel, and to determine the recommended Phase 3 dose of bemarituzumab monotherapy and in combination with docetaxel.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
108 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Bemarituzumab Monotherapy and Combination With Docetaxel in Subjects With Squamous-Cell Non-Small-Cell Lung Cancer (FORTITUDE-201)
Actual Study Start Date :
Mar 29, 2022
Anticipated Primary Completion Date :
Feb 16, 2024
Anticipated Study Completion Date :
Jul 11, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Combination Dose Exploration

Participants with SqNSCLC will receive escalating doses of bemarituzumab in combination with docetaxel.

Drug: Bemarituzumab
Intravenous (IV) infusion
Other Names:
  • AMG 552

    • Drug: Docetaxel
    IV infusion
    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: Bemarituzumab
    Intravenous (IV) infusion
    Other Names:
  • AMG 552

    • Drug: Docetaxel
    IV infusion
    Experimental: Part 3: Bemarituzumab Monotherapy

    Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.

    Drug: Bemarituzumab
    Intravenous (IV) infusion
    Other Names:
  • AMG 552

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [Cycle 1 Day 1 to Cycle 1 Day 21 (cycle is 21 days)]

    2. Parts 1, 2 and 3: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [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)]

      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.

    Secondary Outcome Measures

    1. Parts 1, 2 and 3: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [Part 1/2: 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)]

    2. Parts 1, 2 and 3: Maximum Observed Concentration (Cmax) of Bemarituzumab [Part 1/2: 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)]

    3. Parts 1, 2 and 3: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [Part 1/2: 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)]

    4. Parts 1, 2 and 3: Objective Response Rate [Up to approximately 2 years]

    5. Parts 1, 2 and 3: Duration of Response [Up to approximately 2 years]

    6. Parts 1, 2 and 3: Disease Control Rate [Up to approximately 2 years]

    7. Parts 1, 2 and 3: Progression Free Survival [Up to approximately 2 years]

    8. Parts 1, 2 and 3: Overall Survival [Up to approximately 2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • 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 and 3 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California at Irvine Medical Center Orange California United States 92868
    2 Morristown Medical Center Morristown New Jersey United States 07960
    3 Montefiore Einstein Center for Cancer Care Bronx New York United States 10461
    4 Cliniques Universitaires Saint Luc Bruxelles Belgium 1200
    5 Universitair Ziekenhuis Antwerpen Edegem Belgium 2650
    6 Universitair Ziekenhuis Gent Gent Belgium 9000
    7 Jessa Ziekenhuis - Campus Virga Jesse Hasselt Belgium 3500
    8 Institut Bergonie Bordeaux France 33076
    9 Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie Poitiers France 86021
    10 Institut Gustave Roussy Villejuif France 94805
    11 National Cancer Center Hospital East Kashiwa-shi Chiba Japan 277-8577
    12 Shizuoka Cancer Center Sunto-gun Shizuoka Japan 411-8777
    13 Wakayama Medical University Hospital Wakayama-shi Wakayama Japan 641-8510
    14 Seoul National University Bundang Hospital Seongnam-si, Gyeonggi-do Korea, Republic of 13620
    15 Asan Medical Center Seoul Korea, Republic of 05505
    16 Przychodnia Lekarska Komed Roman Karaszewski Konin Poland 62-500
    17 Pratia MCM Krakow Krakow Poland 30-510
    18 Instytut Centrum Zdrowia Matki Polki Lodz Poland 93-338
    19 Instytut Genetyki i Immunologii GENIM Spzoo Lublin Poland 20-609
    20 Mazowieckie Centrum Leczenia Otwock Poland 05-400
    21 Hospital Universitari Vall d Hebron Barcelona Cataluña Spain 08035
    22 Hospital Universitario Puerta de Hierro Majadahonda Majadahonda Madrid Spain 28222
    23 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    24 Hospital Universitario 12 de Octubre Madrid Spain 28041
    25 National Cheng Kung University Hospital Tainan Taiwan 70403

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT05267470
    Other Study ID Numbers:
    • 20210102
    • 2021-004058-47
    First Posted:
    Mar 4, 2022
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Amgen
    Squamous-Cell Non-Small-Cell Lung Cancer
    FGFR2b-positive Squamous-Cell Non-Small-Cell Lung Cancer
    SqNSCLC
    Bemarituzumab
    Docetaxel
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Docetaxel
    Bemarituzumab

    Study Results

    No Results Posted as of Jul 28, 2022