The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 when
administered as a single agent and in combination with nivolumab in participants with locally
advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile
of ASP1948 when administered as a single agent and in combination with nivolumab and
determine the recommended Phase 2 dose (RP2D) of ASP1948 when administered as a single agent
and in combination with nivolumab. This study will also evaluate the antitumor effect of
ASP1948 when administered as a single agent and in combination with nivolumab.
This is a dose-escalation and expansion study of ASP1948 as a single agent and in combination
with nivolumab. The study consists of 3 periods for monotherapy and combination therapy:
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 from the last dose of study drug.
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, pancreatic cancer and breast
cancer, as well as any tumor types that respond to study drug treatment during dose
- 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
- 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 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
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.) Note: Growth factors, colony stimulating factors
are not permitted in the screening period.
- 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
- 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
- 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
- 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.
Note: This does not apply to subjects with mCRPC who do not have measurable disease.
- Subject is an appropriate candidate for tumor biopsy and consents to undergoing a
tumor biopsy (core needle biopsy or excision) during the treatment period. Note: This
does not apply to subjects with mCRPC who do not have measurable disease.
- Subject meets one of the following:
- Subject has the tumor type for which a confirmed response was observed in a
monotherapy or in combination with nivolumab dose escalation or RP2D cohort; or
- For an expansion cohort opened due to achieving predicted efficacious exposure,
subject has squamous cell carcinoma of the head and neck (SCCHN); or
- For RP2D monotherapy or in combination with nivolumab expansion cohorts, subject
has NSCLC, mCRPC, ovarian, pancreatic, or breast cancer.
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 or ASP1948 in combination with
nivolumab 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 their initial treatment with ASP1948 or ASP1948 in
combination with nivolumab.
- Subject did not receive any prohibited anti-cancer treatment since the last dose of
ASP1948 or ASP1948 in combination with nivolumab.
- Subject did not experience a toxicity that met the discontinuation criteria during the
initial treatment with ASP1948 or ASP1948 in combination with nivolumab.
- 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 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. Note: Corticosteroids for prophylaxis (e.g., contrast
dye allergy) or for brief treatment of conditions not related to study treatment
(e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is also
- 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
- 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 nivolumab or severe hypersensitivity reaction to treatment with another
- 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)). Hepatitis C RNA testing is not required in subjects with
negative Hepatitis C antibody testing. Hepatitis B virus antibodies are not required
in subjects with negative Hepatitis B surface antigen.
- 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
- Subject has an uncontrolled intercurrent illness including, but not limited to cardiac
arrhythmia or psychiatric illness/social situations that would limit compliance with
- 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
- 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
- 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 initiated new 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. Note: If the subject
started receiving such medications more than 28 days prior to the start of study
treatment and needs to continue, this is allowed. However, new anticoagulation may not
be initiated within 28 days prior to the start of study treatment.
- Subject has any condition that makes the subject unsuitable for study participation.
Additional Exclusion Criteria for Re-treatment:
- Subjects who have completed 40 weeks of follow-up with disease control are not
eligible for retreatment.
- Subject currently has an ongoing Adverse Event (AE) related to the initial ASP1948 or
ASP1948 in combination with nivolumab treatment that meets the criteria for treatment
interruption or discontinuation.