A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors

This is a dose-escalation and expansion study of ASP1948. 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 ASP1948 in participants with
locally advanced (unresectable) or metastatic solid tumor malignancies.

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.

For dose expansion, the tumor-specific cohorts will include participants with squamous cell
carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), metastatic
castration-resistant prostate cancer (mCRPC), ovarian cancer, melanoma and breast cancer, as
well as any tumor types that respond to study drug treatment during dose escalation.

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, and has received all standard therapies (unless
the therapy is contraindicated or intolerable) felt to provide clinical benefit.

- 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) mutation-positive non-small cell lung cancer
(NSCLC) is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) therapy until 4
days prior to the start of study drug administration.

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

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

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

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

- Subject has adequate organ function as indicated by laboratory values. (If a subject
has received a recent blood transfusion, the laboratory tests must be obtained ≥ 28
days after any blood transfusion.)

- Female subject must either:

- Be of non-childbearing potential: post-menopausal (defined as at least 1 year
without any menses for which there is no other obvious pathological or
physiological cause) prior to screening, or; documented surgically sterile (e.g.,
hysterectomy, bilateral salpingectomy, bilateral oophorectomy).

- Or, if of childbearing potential: Agree not to try to become pregnant during the
study treatment and for 6 months after the final study drug administration; and
have a negative urine or serum pregnancy test prior to study drug administration;
and if heterosexually active, agree to consistently use 1 form of highly
effective birth control starting at screening and throughout the study treatment
and 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 sexually active male subject with female partner(s) who are of childbearing
potential is eligible if :

- The male subject agrees to use a male condom starting at screening and continues
throughout the study treatment, and for 6 months after the final study drug
administration.

- The male subject has not had a vasectomy or is not sterile, as defined below and
the subject's female partner(s) is utilizing 1 form of highly effective birth
control starting at screening and continuing throughout the study treatment and
for 6 months after the final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
treatment, and for 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 treatment 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 8 to 56 days prior to first dose of study treatment.

- Subject with squamous cell carcinoma of the head and neck (SCCHN), melanoma and breast
cancer, is an appropriate candidate for tumor biopsy and consents to undergoing a
tumor biopsy (core needle biopsy or excision) during the treatment period.

Additional Inclusion Criteria for Re-treatment:

Subjects may be eligible for study drug re-treatment if the study remains open and the
subject continues to meet all of the eligibility criteria above (except prior use of this
drug) and the following conditions:

- Subject stopped initial treatment with ASP1948 after attaining a confirmed CR or PR or
SD.

- Subject experienced a confirmed disease progression by iRECIST (iCPD) (or unconfirmed
progressive disease by iRECIST (iUPD) if subject is not clinically stable to await
confirmatory scan) after stopping the subjects initial treatment with ASP1948.

- Subject did not receive any prohibited anti-cancer treatment since the last dose of
ASP1948.

- Subject did not experience a toxicity that met the discontinuation criteria during the
initial treatment with ASP1948.

Exclusion Criteria:

- Subject weighs < 45 kg.

- Subject has received investigational therapy (other than an investigational epidermal
growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in a subject with EGFR
mutations) 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 the subject is
clinically stable and has no evidence of CNS progression by imaging for at least 28
days 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 14 days.

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

- Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus,
stable endocrinopathies 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 ASP1948 or severe hypersensitivity reaction to treatment with another monoclonal
antibody.

- Subject with positive Hepatitis B virus antibodies and surface antigen (indicating
acute Hepatitis B virus (HBV) or chronic HBV) or Hepatitis C (HCV ribonucleic acid
(RNA) (qualitative); subject with negative Hepatitis C antibody testing may not need
RNA testing.

- Subject has received a live vaccine against infectious diseases within 28 days prior
to initiation of study treatment.

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

- Subject has an active infection requiring systemic therapy (e.g., intravenous
antibiotics) within 14 days prior to study drug treatment.

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

- Subject has an uncontrolled intercurrent illness including, but not limited to cardiac
arrhythmia or psychiatric illness/social situations that would limit compliance with
study requirements.

- Subject's AEs (excluding alopecia) from prior therapy have not improved to Grade 1 or
baseline within 14 days prior to start of study treatment.

- Subject has significant cardiovascular disease including:

- Subject has inadequately controlled hypertension (defined as systolic blood
pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive
medications).

- Subject has a history of myocardial infarction or unstable angina within 6 months
prior to day 1.

- Subject has New York Heart Association Class II or greater chronic heart failure
(CHF).

- History of cerebrovascular accident (CVA) or transient ischemic attack (TIA)
within 6 months prior to study treatment.

- Subject has significant vascular disease (e.g., aortic aneurysm requiring
surgical repair or recent peripheral arterial thrombosis) within 6 months prior
to study treatment.

- Subject has a history of hemoptysis (bright red blood of ½ teaspoon or more per
episode) within 12 weeks prior to study treatment.

- Subject has evidence of a bleeding diathesis or significant coagulopathy.

- Subject has inadequate recovery from prior surgical procedure or has had a major
surgical procedure, open biopsy or significant traumatic injury within 28 days prior
to day 1, or anticipates the need for a major surgical procedure during the course of
the study or minor surgery within 7 days of starting study treatment.

- Subject has received treatment with medications that affect the coagulation cascade
with an international normalized ratio (INR) ≥ 2 such as vitamin K antagonists,
heparins and direct thrombin inhibitors or the use of factor Xa inhibitors within 28
days prior to the start of study treatment.

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