Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas

Study Overview
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Brief Summary
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A Phase 1/2a, dose-escalation study of FF-10502-01 in Patients with Advanced Solid Tumors and Lymphomas. A total of up to 9 cohorts will be enrolled in Phase 1 to establish the MTD. Phase 2 will consist of 2 cohorts: Cohort 1 will include subjects with Pancreatic Cancer. Cohort 2 will include subjects with another tumor type enrolled in the Phase 1 dose-escalation phase who have demonstrated Clinical Benefit by Week 16.

Detailed Description
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Subjects will receive doses of FF-10502-01 intravenously (IV) weekly for three weeks, repeated every 28 days (= 1 cycle). Disease assessments, based on computed tomography (CT), magnetic resonance image (MRI), and, for lymphoma, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans, will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease (PD). Subjects who demonstrate clinical benefit will be allowed to continue therapy with FF-10502-01 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

Official Title
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A Phase 1/2a, Dose-escalation Study of FF-10502-01 for the Treatment of Advanced Solid Tumors and Lymphomas

Conditions
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Solid Tumors, Lymphomas

Intervention / Treatment
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* Drug: FF-10502-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age Histologically or cytologically confirmed advanced or metastatic solid tumor or l lymphoma, that is refractory to standard therapy, relapsed after standard therapy, or for which no standard therapy available that is expected to improve survival by at least three months At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, whichever is shorter), radiotherapy, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1) Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 Life expectancy of ≥ 3 months Adequate hematologic parameters without ongoing transfusional support: Hemoglobin (Hb) ≥ 9 g/dL Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L Platelets ≥ 100 x 109 cells/L Adequate renal and hepatic function: Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease ALT/AST ≤ 2.5 times ULN, or < 5 times ULN for subjects with liver metastases QT interval corrected for rate (QTc) ≤ 480 msec on the electrocardiogram (ECG) obtained at Screening Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of study treatment. Ability to provide written informed consent Exclusion Criteria: Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed. Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results Pregnant or breast-feeding

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 1.5x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 2.25x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 3.375x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 5x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 7.5x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 11.25x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 16.875x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 1: 25x lowest dose of FF-10502-01<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 2a: FF-10502-01 at MTD in Pancreatic Cancer<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |
| Experimental: Phase 2a: FF-10502-01 at MTD in Solid Tumors<br>FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision. | Drug: FF-10502-01<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) | Safety and tolerability assessed by adverse events (AEs), and serious adverse events. (SAEs) | 33 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of overall response rates | Determination of overall response rates | Responses assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug (every 28 days=1 cycle). | 
| Determination of duration of response. | duration of response is determined | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug | 
| Determination of duration of stable disease (SD) as measured from time of 1st evidence of response to time of 1st evidence of progressive disease as measured by CT or MRI. | measurement of stable disease | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug | 
| Evaluate progression-free survival (PFS) | measurement of PFS | Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug | 
| Evaluate overall survival (OS) | measurement of OSS | Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug | 
| Evaluate the mean plasma concentrations of FF-10502-01 | measurement of plasma concentrations | Assessed at Cycle 1 Day 1, and Cycle 1 Day 15 | 
| Evaluate FF-10502-01 incorporation into whole blood cellular DNA by LC-MS/MS as a pharmacodynamic marker | measurement of cellular DNA | Assessed at Cycle 1 Day 1, Cycle 1 Day , Cycle 1 Day 15, Cycle 1, Day 22, Cycle 2 Day 1, at the end of Cycle 2 and ever 2 cycles thereafter up to 24 weeks. |