Clinical trial NCT05267470: A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Squamous-Cell Non-Small-Cell Lung Cancer
Keywords: Squamous-Cell Non-Small-Cell Lung Cancer
FGFR2b-positive Squamous-Cell Non-Small-Cell Lung Cancer
SqNSCLC
Bemarituzumab
Docetaxel
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-03-04
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4
timeFrame: Day 1 to Day 21 of Cycle 1 (each cycle was 21 days)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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 outcomes:
measure: Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax) of Bemarituzumab
timeFrame: 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
measure: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab
timeFrame: Pre-dose Cycle 2 Day 1 and Cycle 3 day 1
measure: Percentage of Participants Who Achieved an Objective Response (OR)
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: 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)
measure: Progression-free Survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Cancer Institute
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bron Cedex
country: France
facility: CHU de Lyon - Hopital Louis Pradel
city: Paris Cedex 20
country: France
facility: Hôpital Tenon
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Konin
country: Poland
facility: Przychodnia Lekarska Komed Roman Karaszewski
city: Krakow
country: Poland
facility: Pratia Mcm Krakow
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne Sp zoo
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lublin
country: Poland
facility: Instytut Genetyki i Immunologii GENIM Spzoo
city: Lublin
country: Poland
facility: Centrum Medyczne Hope Clinic Sebastian Szklener
city: Otwock
country: Poland
facility: Mazowieckie centrum leczenia
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
state: Andalucía
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Hospitalet de Llobregat
country: Spain
facility: Institut Catala d Oncologia Hospitalet. Hospital Duran i Reynals
state: Cataluña
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña Hospital Teresa Herrera
state: Galicia
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: