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

Phase 1TerminatedNCT05267470

Amgen74 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Squamous-Cell Non-Small-Cell Lung Cancer

Interventions

BemarituzumabDRUG

Intravenous (IV) infusion

DocetaxelDRUG

IV infusion

PembrolizumabDRUG

IV infusion

Carboplatin

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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

Locations (39)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

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

Data from ClinicalTrials.gov

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