Lymphomas, Solid Tumors
Conditions
Brief summary
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 Maximum Tolerated Dose (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
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.
Interventions
DRUGFF-10502-01
Sponsors
Fujifilm Pharmaceuticals U.S.A., Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Alanine aminotransferase (ALT)/aspartate aminotransferase (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Adverse Events (TEAE) | Each patient was followed from baseline through the treatment period (maximum treatment period up to 38 months) until long-term follow-up was completed (6 mos post end of study) or patient discontinued either by withdrawal, progressive disease or death. | Safety and tolerability assessed by number of subjects with adverse events (AEs), and serious adverse events. (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Overall Response Rates (ORR) | 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), up to 38 months | Number of subjects who had overall responses of Partial Response, Stable Disease, Progressive Disease or Not Evaluable |
| Number of Subjects With Objective Response (OR) Events | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Number of subjects with objective response events, number of subjects with progressive disease or death events atter objective response and number of subjects censored after objective response |
| Median Number of Days of Objective Response (OR) | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Median duration of objective response in days for each cohort". |
| Number of Subjects With Stable Disease (SD) Events | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Number of subjects with stable disease, number of subjects with progressive disease or death after stable disease and number of subjects censored after stable disease |
| Median Number of Days of Stable Disease (SD) | Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Median duration of stable disease (SD) in days for each cohort |
| Number of Subjects With Progression-free Survival (PFS) Events | Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Number of subjects with progressive disease or death and number of subject censored. |
| Median Number of Days of Progression-free Survival (PFS) | Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | This outcome measure shows the median number of days of progression-free survival (PFS) for each cohort |
| Number of Subjects With Overall Survival (OS) Events | Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Number of subjects with overall survival (OS) events in each cohort |
| Median Number of Days of Overall Survival (OS) | Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months | Median number of days of overall survival (OS) for each cohort |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFilip Janku, MD
University of Texas MD Anderson Center
PRINCIPAL_INVESTIGATORGerald Falchook, MD
Sarah Cannon Research Institute-Denver
Participant flow
Recruitment details
Participants were recruited based on physician referral at 2 academic medical centers between January 2016 and November 2020. The first participant was dosed on January 14, 2016 and the last participant was dosed on October 3, 2020. Study completion date was November 5, 2020.
Pre-assignment details
For Phase 1, anticipated enrollment was 40 subjects; 40 subjects were enrolled and treated with FF-10501-01. For Phase 2, anticipated enrollment was 66 subjects; 66 were enrolled and treated with FF-10501-01.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 90 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 1 / 7 | 2 / 3 | 5 / 9 | 0 / 6 | 3 / 3 | 14 / 19 | 15 / 36 | 1 / 10 | 1 / 1 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 3 / 3 | 9 / 9 | 6 / 6 | 3 / 3 | 19 / 19 | 36 / 36 | 10 / 10 | 1 / 1 |
| serious Total, serious adverse events | 2 / 3 | 0 / 3 | 2 / 3 | 2 / 3 | 5 / 7 | 0 / 3 | 5 / 9 | 5 / 6 | 0 / 3 | 14 / 19 | 20 / 36 | 2 / 10 | 0 / 1 |
Outcome results
None listed