A Study of ASP1951 in Subjects With Advanced Solid Tumors

This is a dose-escalation and expansion study of ASP1951. The study consists of 3 periods:
screening, treatment and follow up, followed by an optional Re-treatment period for
participants that qualify.

The escalation cohorts will evaluate escalating dose levels of ASP1951 in participants with
locally advanced (unresectable) or metastatic solid tumor malignancies including but not
limited to squamous cell carcinoma of the head and neck, colorectal cancer, prostate cancer
and cervical cancer.

For dose expansion, the tumor-specific cohorts will include participants with any tumor types
that respond to study drug treatment during dose escalation.

Participants may reinitiate study drug treatment in the optional Re-treatment period after
confirmation that the participant meets all the re-treatment eligibility criteria.

After discontinuation of study drug, all participants will complete an end-of-treatment
visit, along with 30-day and 90 day safety follow-up visits.

Inclusion Criteria:

- Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no
limit to the number of prior treatment regimens) that is confirmed by available
pathology records or current biopsy as well as the following:

- Subject in the escalation cohort has received all standard therapies (unless the
therapy is contraindicated or intolerable) felt to provide clinical benefit the
subject's specific tumor type. OR

- Subject in an expansion cohort has received at least 1 standard therapy for the
subject's specific tumor type.

- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or
2.

- Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was
at least 21 days prior to initiation of study drug administration. A subject with
epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)
mutation-positive non-small cell lung cancer (NSCLC) is allowed to remain on EGFR
tyrosine kinase inhibitor (TKI) or ALK inhibitor therapy until 4 days prior to the
start of study drug administration.

- Subject has completed any radiotherapy (including stereotactic radiosurgery) at least
2 weeks prior to study drug administration.

- Subject's AEs (excluding alopecia) from prior therapy have improved to grade 1 or
baseline within 2 weeks prior to start of study treatment.

- Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive bone
scan and/or soft tissue disease documented by computed tomography [CT]/magnetic
resonance imaging [MRI]) meets both of the following:

- Subject has serum testosterone ≤ 50 ng/dL at Screening.

- Subject has had a bilateral orchiectomy or plans to continue androgen deprivation
therapy (ADT) for the duration of study treatment.

- Subject has adequate organ function prior to start of study treatment. If a subject
has received a recent blood transfusion, the laboratory tests must be obtained ≥ 4
weeks after any blood transfusion.

- A female subject is eligible to participate if she is not pregnant and at least 1 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 treatment, and for 6 months after the final study drug administration.

- Female subject must not donate ova starting at Screening and throughout the study
treatment, and for 6 months after the final study drug administration.

- A male subject with female partner(s) of childbearing 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
administration.

- Subject agrees not to participate in another interventional study while receiving
study drug (Subjects who are currently in the follow-up period of an interventional
clinical trial are allowed).

Additional Inclusion Criteria for Subjects in the Expansion Cohorts:

- Subject has at least 1 measureable lesion per RECIST 1.1. The measureable lesion must
be outside the field of radiation if subject had prior radiotherapy. Subjects with
mCRPC who do not have measurable lesions must have at least 1 of the following:

- Progression with 2 or more new bone lesions; or

- Prostate-specific antigen (PSA) progression (defined as a minimum of 3 rising PSA
levels with an interval of ≥ 1 week between each determination) within 6 weeks
prior to study drug administration and a PSA value at the screening visit ≥ 2
ng/mL.

- Subject consents to provide available tumor specimen in a tissue block or unstained
serial slides obtained within 56 days prior to first dose of study treatment.

- Subject is an appropriate candidate for tumor biopsy and consents to undergoing a
tumor biopsy (core tissue biopsy or excision) during the treatment period as indicated
in the Schedule of Assessments.

Exclusion Criteria:

- Subject weighs < 45 kg.

- Subject has received investigational therapy (other than an investigational EGFR TKI
in a subject with EGFR activating mutations or ALK inhibitor in a subject with an ALK
mutation) within 21 days prior to start of study drug.

- Subject requires or has received systemic steroid therapy or any other
immunosuppressive therapy within 14 days prior to study drug administration. Subjects
using a physiologic replacement dose of hydrocortisone or its equivalent (defined as
up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg
per day of prednisone) are allowed.

- Subject has symptomatic central nervous system (CNS) metastases or subject has
evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).
Subjects with previously treated CNS metastases are eligible, if they are clinically
stable and have no evidence of CNS progression by imaging for at least 4 weeks prior
to start of study treatment and are not requiring immunosuppressive doses of systemic
steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of dexamethasone, or > 10
mg per day of prednisone or equivalent) for longer than 2 weeks.

- Subject has leptomeningeal disease as a manifestation of the current malignancy.

- Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus,
endocrinopathies stably maintained on appropriate replacement therapy, and skin
disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are
allowed.

- Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3
toxicity that was mechanistically related (e.g., immune related) to the agent.

- Subject has known history of serious hypersensitivity reaction to a known ingredient
of ASP1951 or severe hypersensitivity reaction to treatment with another monoclonal
antibody.

- Subject with positive for Hepatitis B virus (HBV) antibodies and surface antigen
(including acute HBV or chronic HBV) or Hepatitis C ([HCV]; ribonucleic acid [RNA]
detected by qualitative assay). Hepatitis C RNA testing is not required in subjects
with negative Hepatitis C antibody testing.

- Subject has received a live vaccine against infectious diseases within 4 weeks prior
to initiation of study treatment.

- Subject has a history of drug-induced pneumonitis (interstitial lung disease) or
currently has pneumonitis.

- Subject has an infection requiring systemic therapy within 2 weeks prior to study drug
administration.

- Subject has received a prior allogeneic bone marrow or solid organ transplant.

- Subject is expected to require another form of antineoplastic therapy while on study
treatment.

- Subject has had a myocardial infarction or unstable angina within 6 months prior to
the start of study treatment or currently has an uncontrolled illness including, but
not limited to symptomatic congestive heart failure, clinically significant cardiac
disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.

- Subject has received prior treatment with an anti-glucocorticoid-induced tumor
necrosis factor receptor (GITR) antibody.

- Subject has had a major surgical procedure and has not completely recovered within 28
days prior to the start of study treatment.

- Subject has any condition which makes the subject unsuitable for study participation.