The purpose of this study is to evaluate the safety and tolerability of ASP1235 (AGS62P1)
given at three dosing schedules (Schedule A, every three weeks [Q3W] or Schedule B, every
other week of a 4 week cycle [Q2W] or Schedule C once a week for 3 weeks of a 4 week cycle)
in subjects with acute myeloid leukemia (AML) and determine the maximum tolerated dose (MTD).
In addition, this study will assess the pharmacokinetics (PK), the immunogenicity and the
anti-leukemic activity of ASP1235 (AGS62P1).
- Subject has morphologically documented primary or secondary AML by the World Health
Organization (WHO) criteria (2008) which is relapsed or refractory after failing at
least 1 regimen and is not a candidate for established salvage treatment regimens. For
expansion cohorts, patients are eligible if they have had ≤ 3 prior lines of therapy.
Lines of therapy include initial induction (up to 2 cycles) with
consolidation/maintenance, if applicable, and subsequent salvage regimens.
Consolidation alone and stem cell transplantation are not counted as lines of therapy.
- Subject has an Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
- Subject has adequate renal function with an estimated creatinine clearance of ≥ 30
mL/min by the Cockcroft-Gault equation adjusted for body weight
- Subject has a total bilirubin ≤ 1.5 x upper limit of normal (ULN), albumin ≥ 2.5 g/d,
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper
limit of normal (ULN)
- Subjects must be competent to comprehend, provide written informed consent, and date
an independent ethics committee/institutional review board/research ethics board
(IEC/IRB/REB) approved informed consent form
- A female subject is eligible to participate if she is not pregnant and at least one of
the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment
period and for at least 6 months after the final study drug administration.
- Female subject must agree not to breastfeed starting at screening and throughout the
study period, and for 6 months after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the study
period, and for 6 months after the final study drug administration.
- A male subject with female partner(s) of child-bearing potential must agree to use
contraception during the treatment period and for at least 6 months after the final
study drug administration.
- A male subject must not donate sperm during the treatment period and for at least 6
months after the final study drug administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period and for 6 months after the final study drug
- Subject has a diagnosis of acute promyelocytic leukemia (APL)
- Subject has preexisting sensory or motor neuropathy Grade ≥ 2 at baseline
- Subject has received small molecule therapy, radiotherapy, immunotherapy, monoclonal
antibodies, investigational drug, or chemotherapy within 14 days before first dose of
study drug, with the exception of hydroxyurea
- Subject has any Grade ≥ 2 persistent non-hematological toxicity related to
- Subject with Graft vs. Host Disease (GVHD) who is receiving treatment with systemic
glucocorticoids > 10 mg/day equivalent of prednisone; however, treatment with low dose
glucocorticoids (≤ 10 mg/day equivalent of prednisone) is permitted
- The use of systemic glucocorticoids in excess of 10 mg/day equivalent of
prednisone is permitted provided it is not for the treatment of GVHD (e.g.
chronic obstructive pulmonary disease, anti-emetic, infusion reactions). The
chronic use of topical, inhaled, and locally injected steroids is permitted
- Subject has known current central nervous system (CNS) disease
- Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart
Association CHF Functional Classification System) or clinically significant cardiac
disease within 12 months of the first dose of study drug, including myocardial
infarction, unstable angina, Grade 2 or greater peripheral vascular disease,
congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by
- Subject has clinical evidence of Disseminated Intravascular Coagulation
- Subject has known positivity for human immunodeficiency virus
- Subject has known active hepatitis B (positive hepatitis B surface antigen [HBs Ag])
or C infection. For subjects who are negative for HBs Ag, but hepatitis B core
antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed
and if positive, the subject will be excluded. Subjects with positive serology but
negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible.
- Subject has an uncontrolled active infection requiring treatment and grade 3 or higher
fever 48 hours before the first dose of study drug. Controlled infections (i.e. 3
negative cultures completing antibiotics and/or stable fungal infection in therapy)
are allowed provided the subject has a temperature of < 38.3°C within 48 hours of the
first dose of study drug.
- Subject has a known sensitivity to any of the components of the investigational
product ASP1235 (AGS62P1):
- ASP1235 (AGS62P1)
- L-Histidine base
- L-Histidine HCl
- α, α -Trehalose Dihydrate
- Polysorbate 20
- Major surgery within 28 days of the first dose of study drug
- Subject is pregnant or lactating
- Subject has a condition or situation which may put the subject at significant risk,
may confound the study results, or may interfere significantly with subject's
participation in the study
- Subject has any medical, psychiatric, addictive or other disorder which compromises
the ability of the subject to give written informed consent and/or to comply with
- Subject has ocular condition such as:
- Active infection or corneal ulcer
- History of corneal transplantation
- Contact lens dependent (if using contact lens, must be able to switch to glasses
during the entire study duration)
- Uncontrolled glaucoma (topical medications allowed)
- Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active
uveitis, macular degeneration) requiring surgery, laser treatment, or
- Papilledema or other active optic nerve disorder