Advanced Solid Tumors

Primary: • To evaluate the safety profile of escalating doses of FPA144 in patients with advanced solid tumors, and to determine the MTD and RD (Part 1A only) Secondary: • To characterize the PK profile of single and multiple doses of intravenously administered FPA144 • To evaluate the safety and tolerability of longer term exposure to FPA144 administered • To evaluate the objective response rate (ORR) in patients with FGFR2b-selected gastric or gastroesophageal cancer (Part 2 only) • To evaluate duration of response in responding patients with FGFR2b-selected gastric or gastroesophageal cancer (Part 2 only)

FPA144

FPA144

sterile suspension vials

20

Primary Outcome Measures :
1. Number of Participants With Protocol Specified Dose-limiting Toxicities (Part 1 Only). [ Time Frame: 4 weeks on average ]
Number of participants with grade 3 and grade 4 adverse events (AE) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)

2. Number of Participants With AEs and Clinical Laboratory Abnormalities (Parts 1B and 2 Only) [ Time Frame: 16 weeks on average ]
Number of Participants with AEs and clinical laboratory abnormalities (Parts 1B and 2 only)


Secondary Outcome Measures :
1. Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration [ Time Frame: 16 weeks on average ]
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,

2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: 16 weeks on average ]
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.

3. Duration of Response Per RECIST 1.1 (Part 2 Only) [ Time Frame: 16 weeks on average ]
Duration of complete or partial response with 95% confidence intervals in gastric cancer population.

4. Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve [ Time Frame: 16 weeks on average ]
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,

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
o Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment
o Histologically or cytologically confirmed transitional cell carcinoma of the genitourinary tract
o 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 • 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