A Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With a PD-l Inhibitor (Nivolumab or Pembrolizumab) in Subjects With Advanced Solid Tumors

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, or 1.

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.) Subjects can be on a stable dose of erythropoietin (≥ approximately 3 months). 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.

* 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).

Subject has at least 1 measurable lesion per RECIST 1.1. The measureable lesion must be outside the field of radiation if subject had prior radiotherapy. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 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. 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

* ASP1948 monotherapy or in combination with pembrolizumab expansion cohort is opened due to achieving predicted efficacious exposure, subject has squamous cell carcinoma of the head and neck (SCCHN); or

* RP2D monotherapy cohort is opened and subject has NSCLC, mCRPC, ovarian cancer, pancreatic cancer or breast cancer; or

* RP2D combination with pembrolizumab expansion cohort, is opened and subject has NSCLC (all PD-L1 status), NSCLC PD-L1 high\*, ovarian cancer, colorectal cancer, or breast cancer.

* NSCLC with PD-L1 high expressing tumor as determined by immunohistochemistry at a central laboratory during the screening period.

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 or pembrolizumab after attaining a confirmed CR or PR or SD.

Subject experienced a confirmed disease progression by iRECIST (iCPD) after stopping their initial treatment with ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.

Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.

Subject did not experience a toxicity that met the discontinuation criteria during the initial treatment with ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.

What this study is about