The purpose of this study is to establish the recommended phase 2 dose (RP2D) of ASP1650
(Safety Lead-in Phase), as well as, evaluate the efficacy of ASP1650 as measured by confirmed
objective response rate (ORR) (phase 2) in participants with incurable platinum refractory
germ cell tumors.
This study will also evaluate the following efficacy measures for confirmed objective
response rate (ORR); clinical benefit rate (CBR); duration of response (DOR); and
progression-free survival (PFS); as well as safety and tolerability; the effect of ASP1650 on
changes in serum beta human chorionic gonadotropin (βhCG) and alpha-fetoprotein (AFP); and
the pharmacokinetics of ASP1650.
The study consists of 2 phases: Safety Lead-in phase and phase 2. The Safety Lead-in phase of
this study is to establish the tolerability of RP2D. Nine to 18 participants will be enrolled
in the Safety Lead-in phase. The RP2D determination will be based on at least 6 evaluable
participants at the RP2D as determined by the Dose Evaluation Committee (DEC).
Once RP2D has been established as tolerable, up to 34 participants including participants
from the RP2D cohort of the Safety Lead-in phase will be enrolled in phase 2 to receive
ASP1650 for up to a maximum of 12 cycles or until a study discontinuation criteria has been
met, whichever occurs earlier.
- 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.
- Subject must not donate sperm during the treatment period and for 6 months after the
final study treatment administration.
- A 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
- Subject agrees not to participate in another interventional study while receiving
study drug in present study.
Disease Specific Criteria:
- Subject has histological evidence of germ cell tumor.
- Subject must have a germ cell tumor that is not amenable to cure with either surgery
- Subjects with seminoma and non-seminoma are eligible.
- Subject must have received initial cisplatin based combination chemotherapy AND
demonstrated progression following at least 1 salvage regimen for advanced germ cell
neoplasm (including relapsed primary mediastinal nonseminomatous germ cell tumor).
- Initial cisplatin based combination therapy includes
etoposide-ifosfamide-cisplatin or similar regimens
- "Salvage" regimens include high dose chemotherapy,
paclitaxel-ifosfamidecisplatin, vinblastine-ifosfamide cisplatin or similar
- "Failure" of prior therapy is defined as: A > 25% increase in the products of
perpendicular diameters of measurable tumor masses during prior therapy, which
are not amenable to surgical resection; OR the presence of new tumor that are not
amenable to surgical resection; OR an increase in alpha-fetoprotein (AFP) or beta
human chorionic gonadotropin (βhCG) (≥ 50% increase in 2 separate samples
collected at least 1 week apart are required if rising tumor markers are the only
evidence of failure). NOTE: Subjects with clinically growing teratoma (enlarging
mature teratoma arising during or after chemotherapy for a non seminomatous
germ-cell tumor and with normal serum levels of AFP and βhCG) should undergo
surgical resection if feasible.
- Subjects with late relapse (> 2 years) not amenable to resection are eligible.
- Subjects must have evidence of recurrent or metastatic carcinoma by 1 or more of the
- Subject has measurable disease according to Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 within 28 days prior to the first dose of study treatment.
For subjects with only 1 measurable lesion and prior radiotherapy, the lesion
must be outside the field of prior radiotherapy or must have documented
progression following radiation therapy.
- Subject has a baseline rising tumor marker (AFP or βhCG). NOTE: If a rising tumor
marker is the only evidence of progressive disease, at least 2 consecutive rising
values at least 1 week apart are needed. Subjects with only evidence of disease
as rising tumor marker AFP and βhCG will be assessed for alternate causes of
increased serum levels of these markers, such as cross reaction with luteinizing
hormone (LH) (can be tested if needed by testosterone suppression of LH),
hepatitis, use of marijuana or second primary tumor.
Physical or Laboratory Findings:
- Subject must have an available tumor specimen in a tissue block or unstained serial
slides, or subject is an appropriate candidate for tumor biopsy and is amenable to
undergoing a tumor biopsy during the screening period.
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Subject must meet all of the following criteria based on the centrally analyzed
laboratory tests within 14 days prior to the first dose of study treatment. In case of
multiple central laboratory data within this period, the most recent data should be
used to determine eligibility.
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
- Platelets ≥ 75 x 109/L
- Albumin ≥ 2.5 g/dL
- Total bilirubin ≤ 2 x upper limit of normal (ULN) or direct bilirubin ≤ ULN for
subjects with total bilirubin levels > 2 x ULN
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
without liver metastases (or ≤ 5 x ULN if liver metastases are present) Either
serum creatinine ≤ 2.5 x ULN or estimated glomerular filtration rate ≥ 30
- Prothrombin time/international normalized ratio (PT/INR) and partial
thromboplastin time (PTT) ≤ 2 x ULN (except for subjects receiving
Prohibited Treatment or Therapies:
- Subject has received systemic immunosuppressive therapy, including systemic
corticosteroids within 14 days prior to first dose of study treatment. Subject using a
physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30
mg per day of hydrocortisone or up to 10 mg per day of prednisone) is eligible.
Subject who received systemic steroids for asymptomatic central nervous system (CNS)
metastases within 14 days prior to first dose of study treatment is eligible.
- Subject has received other investigational agents or devices within 28 days prior to
first dose of study treatment.
- Subject has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to
study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse
event (AE) due to monoclonal antibody (mAb) agents administered more than 4 weeks
- Subject has had prior chemotherapy, targeted small molecule therapy, or radiation
therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 2
or at baseline) from AEs due to a previously administered agent.
Medical History or Concurrent Disease:
- Subject has prior severe allergic reaction or intolerance to a monoclonal antibody,
including humanized or chimeric antibodies requiring permanent discontinuation.
- Subject has known immediate or delayed hypersensitivity, intolerance or
contraindication to any component of study treatment.
- Subject has an active human immunodeficiency virus (HIV) infection or known active
hepatitis B (HBsAg) or C infection. Subjects with well-controlled HIV infections
(i.e., without detectable viral load) are eligible. For subjects who are negative for
HBsAg, but hepatitis B core antibody (HBcAb) positive, an HBsAg 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 active infection requiring systemic therapy that has not completely
resolved within 14 days prior to first dose of study treatment.
- Subject has symptomatic central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subject with asymptomatic CNS metastases is eligible.
- Subject has had a major surgical procedure and has not completely recovered within 28
days prior to the first dose of study treatment.
- Subject has psychiatric illness or social situations that would preclude study
- Subject has another malignancy for which treatment is required. Subject with
negligible risk of metastasis or death is eligible (e.g., basal or squamous cell skin
cancer, localized prostate cancer treated with curative intent or incidental prostate
cancer T1-T2a, Gleeson ≤ 3 + 4, PSA ≤ 0.5 and who are undergoing active surveillance).
- Subject has any concurrent disease, infection, or co-morbid condition that interferes
with the ability of the subject to participate in the study, which places the subject
at undue risk or complicates the interpretation of data.