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

NCT05267470 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 202101022021-004058-472023-505456-22
• Study Type: interventional
• Target: 74
• Locations: 8 countries
• Sites: 39

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab

  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

  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

  Pre-dose Cycle 2 Day 1 and Cycle 3 day 1

• Percentage of Participants Who Achieved an Objective Response (OR)

  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)

  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)

Study Arms (4)

Part 1: Combination Dose Exploration

EXPERIMENTAL

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

Drug: Bemarituzumab; Drug: Docetaxel

Part 2: Combination Dose Expansion

EXPERIMENTAL

Participants with SqNSCLC and FGFR2b overexpression will receive the dose of bemarituzumab in combination with docetaxel identified as safe during Part 1.

Drug: Bemarituzumab; Drug: Docetaxel

Part 3: Bemarituzumab Monotherapy

EXPERIMENTAL

Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.

Drug: Bemarituzumab

Part 4: Combination Immuno-chemotherapy

EXPERIMENTAL

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: Bemarituzumab; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel

Interventions

Bemarituzumab DRUG

Intravenous (IV) infusion

Also known as: AMG 552

Part 1: Combination Dose Exploration; Part 2: Combination Dose Expansion; Part 3: Bemarituzumab Monotherapy; Part 4: Combination Immuno-chemotherapy

Docetaxel DRUG

IV infusion

Part 1: Combination Dose Exploration; Part 2: Combination Dose Expansion

Pembrolizumab DRUG

IV infusion

Part 4: Combination Immuno-chemotherapy

Carboplatin DRUG

IV infusion

Part 4: Combination Immuno-chemotherapy

Paclitaxel DRUG

IV infusion

Part 4: Combination Immuno-chemotherapy

Nab-paclitaxel DRUG

IV infusion

Part 4: Combination Immuno-chemotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (39)

University of California Irvine

Orange, California, 92868, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

University of Pittsburgh, Cancer Institute

Pittsburgh, Pennsylvania, 15211, United States

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, 3500, Belgium

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHU de Lyon - Hopital Louis Pradel

Bron, 69677, France

Location

Hôpital Tenon

Paris, 75020, France

Location

Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie

Poitiers, 86021, France

Location

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou

Rennes, 35033, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

Przychodnia Lekarska Komed Roman Karaszewski

Konin, 62-500, Poland

Location

Pratia Mcm Krakow

Krakow, 30-727, Poland

Location

Krakowskie Centrum Medyczne Sp zoo

Krakow, 31-501, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

Instytut Genetyki i Immunologii GENIM Spzoo

Lublin, 20-609, Poland

Location

Centrum Medyczne Hope Clinic Sebastian Szklener

Lublin, 20-701, Poland

Location

Mazowieckie centrum leczenia

Otwock, 05-400, Poland

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Regional Universitario de Malaga

Málaga, Andalusia, 29011, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Institut Catala d Oncologia Hospitalet. Hospital Duran i Reynals

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

Location

Complexo Hospitalario Universitario A Coruña Hospital Teresa Herrera

A Coruña, Galicia, 15006, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

bemarituzumab; Docetaxel; pembrolizumab; Carboplatin; Paclitaxel; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 4, 2022
• Study Start: March 29, 2022
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: March 25, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

KR (3); BE (4); JP (3); TW (3); PL (7); FR (6); US (4); ES (9)