Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a three-part, open-label, safety, tolerability, and PK study of FPA144. Patients will be enrolled in Part 1 (A or B, dose escalation) or Part 2 (dose expansion) of the study, but not both.

Detailed Description
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Part 1A is a dose-escalation study in patients with any locally advanced or metastatic solid tumor or lymphoma for which standard therapies have been exhausted. Part 1B will further assess safety and evaluate PK of FPA144 in gastric cancer patients. Part 2 patients will be enrolled and treated in order to further characterize safety and preliminary efficacy in a selected cancer patient population with the greatest potential for clinical benefit from FPA144 treatment.

Official Title
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A Phase 1 Open-Label, Dose-Finding Study Evaluating Safety and Pharmacokinetics of FPA144 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, Gastric Cancer, Transitional Cell Carcinoma of the Bladder

Intervention / Treatment
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* Drug: FPA144


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy of at least 3 months ECOG performance status of 0 to 1 • In sexually-active patients, willingness to use 2 effective methods of contraception Adequate hematological and organ function, confirmed by lab values Tumor tissue must be available for prospective determination of FGFR2b overexpression Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment Histologically or cytologically confirmed transitional cell carcinoma of the genitourinary tract Measurable disease as defined by RECIST version 1.1 Exclusion Criteria: Untreated or symptomatic central nervous system (CNS) metastases Impaired cardiac function or clinically significant cardiac disease - Treatment with any anticancer therapy or participation in another therapeutic clinical study with investigational drugs </=14 days (</=28 days for patients in Korea) prior to first dose of FPA144 Ongoing acute adverse effects from prior anticancer or investigational therapy > NCI CTCAE Grade 1 Retinal disease or a history of retinal disease or detachment Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea Major surgical procedures are not allowed ≤28 days prior to FPA144 administration Females who are pregnant or breastfeeding; women of childbearing potential must not be considering getting pregnant during the study - Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study Known allergy or hypersensitivity to components of the FPA144 formulation including polysorbate History of prior malignancy except: a) Curatively treated non-melanoma skin cancer or b) Solid tumor treated curatively more than 5 years previously without evidence of recurrence or c) History of other malignancy that in the Investigator's opinion would not affect the determination of study treatment effect Prior treatment with any selective inhibitor (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the FGF-FGFR pathway

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A: FPA144 Dose Escalation Solid Tumors<br>Dose escalation of FPA144 (0.3 mg/kg to 15 mg/kg) | Drug: FPA144<br>* FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.<br>* Other names: Bemarituzumab;|
| Experimental: Part 1B: FPA144 Dose Escalation Gastric Cancer<br>Dose escalation of FPA144 (3-10 mg/kg) in patients with gastric cancer | Drug: FPA144<br>* FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.<br>* Other names: Bemarituzumab;|
| Experimental: Part 2: FPA144 Dose Expansion Gastric or Other Solid Tumors<br>Evaluation of objective responses in patients with tumors with various levels of FGFR2b overexpression | Drug: FPA144<br>* FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.<br>* Other names: Bemarituzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Protocol Specified Dose-limiting Toxicities (Part 1 Only). | Number of participants with grade 3 and grade 4 adverse events (AE) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs) | 4 weeks on average | 
| Number of Participants With AEs and Clinical Laboratory Abnormalities (Parts 1B and 2 Only) | Number of Participants with AEs and clinical laboratory abnormalities (Parts 1B and 2 only) | 16 weeks on average | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration | Sampling following the first dose in Part 1, pre and post-dose at selected cycles, and at the end of treatment for both Part 1 and Part 2. • Summary of area under serum concentration-time curve, maximum serum concentration, | 16 weeks on average | 
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 16 weeks on average | 
| Duration of Response Per RECIST 1.1 (Part 2 Only) | Duration of complete or partial response with 95% confidence intervals in gastric cancer population. | 16 weeks on average | 
| Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve | Sampling following the first dose in Part 1, pre and post-dose at selected cycles, and at the end of treatment for both Part 1 and Part 2. • Summary of area under serum concentration-time curve, maximum serum concentration, | 16 weeks on average | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FGFR2b, FGFR2, FGFR, bladder neoplasms, esophageal cancer