A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC WithFGFR2b Overexpression (FORTITUDE-201)

JRCT ID: jRCT2051220022

Registered date:03/05/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Squamous-Cell Non-Small-Cell Lung Cancer
• Date of first enrollment: 29/03/2022
• Target sample size: 180
• Countries of recruitment: United States,Japan,Belgium,Japan,Poland,Japan,Spain,Japan,France,Japan,Korea,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Part 1: Combination Dose Exploration
Participants with SqNSCLC will receive escalating doses of bemarituzumab in combination with docetaxel.
Interventions:
Drug: Bemarituzumab
Drug: Docetaxel

- 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.
Interventions:
Drug: Bemarituzumab
Drug: Docetaxel

- Experimental: Part 3: Bemarituzumab Monotherapy
Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.
Intervention: Drug: Bemarituzumab

- Experimental: Part 4: Combination Immuno-chemotherapy
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.
Interventions:
Drug: Bemarituzumab
Drug: Pembrolizumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Nab-paclitaxel

Outcome(s)

Primary Outcome

1. Part 1 and 4: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 Day 1 to Cycle 1 Day 21(cycle is 21 days) ]
2. Parts 1, 2, 3 and 4: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Cycle 1Day 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

1. Parts 1, 2, 3 and 4: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [ Time Frame: Part 1/2/4: 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, 3 and 4: Maximum Observed Concentration (Cmax) of Bemarituzumab [ Time Frame: Part 1/2/4: 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, 3 and 4: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [ Time Frame: Part 1/2/4: 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, 3 and 4: Objective Response Rate [ Time Frame: Up to approximately 2 years ]
5. Parts 1, 2, 3 and 4: Duration of Response [ Time Frame: Up to approximately 2 years ]
6. Parts 1, 2, 3 and 4: Disease Control Rate [ Time Frame: Up to approximately 2 years ]
7. Parts 1, 2, 3 and 4: Progression Free Survival [ Time Frame: Up to approximately 2 years ]
8. Parts 1, 2, 3 and 4: Overall Survival [ Time Frame: Up to approximately 2 years ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 99age old
• Gender: Both

Include criteria

1. Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
2. Age >= 18 years old (or legal adult within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed
3. Pathologically confirmed squamous cell lung carcinoma
4. Disease that is unresectable, locally advanced or metastatic (not amenable to curative therapy)
5. 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
6. 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 aplatinum-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.
7. 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.
8. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10 Adequate organ function as determined per protocol
11. Part 2, 3 and 4 only: FGFR2b overexpression as determined by centrally performed immunohistochemistry (IHC) testing

Exclude criteria

1. Mixed small-cell lung cancer or mixed non-small cell lung cancer (NSCLC) histology
2. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly
4. 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 >160mmHg 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
5. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
6. 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
7. Part 1 and Part 2: participants that experienced toxicity or hypersensitivity requiring discontinuation of prior docetaxel treatment
8. Part 1 only: participants that had disease progression on prior therapy with docetaxel
9. 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)
10. Prior treatment with any selective inhibitor of the fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) pathway

Related Information

• Primary Sponsor: Kaneda Hirokazu
• Secondary ID(s): NCT05267470