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

Amgen

Status and phase: Terminated; Phase 1

Conditions: Squamous-Cell Non-Small-Cell Lung Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05267470

2021-004058-47 (EudraCT Number)

20210102

2023-505456-22 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

74 participants in 4 patient groups

Part 1: Combination Dose Exploration

Experimental group

Description:

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

Treatment:

Drug: Bemarituzumab

Drug: Docetaxel

Part 2: Combination Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: Bemarituzumab

Drug: Docetaxel

Part 3: Bemarituzumab Monotherapy

Experimental group

Description:

Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.

Treatment:

Drug: Bemarituzumab

Part 4: Combination Immuno-chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Bemarituzumab

Drug: Pembrolizumab

Drug: Nab-paclitaxel

Drug: Carboplatin

Drug: Paclitaxel