Prexasertib and Anti-PD-L1 Monoclonal Antibody LY3300054 in Treating Patients with Metastatic or Unresectable Solid Tumors

Inclusion Criteria

• Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care.
• Patients must have histologically confirmed solid tumor that is metastatic or unresectable, and there is no available therapy likely to convey clinical benefit.
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Measurable disease is defined as at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
• Patients must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study (except alopecia).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Absolute neutrophil count >= 1,500/mcL.
• Platelets >= 100,000/mcL.
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN.
• Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min by Cockcroft-Gault equation for participants with creatinine levels above institutional normal.
• Free T4 within institutional normal limits.
• The effects of prexasertib and LY3300054 on the developing human fetus are unknown. For this reason, women of childbearing potential and male patients with partners of childbearing potential must agree to use two highly effective forms of contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of prexasertib and LY3300054 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Women of childbearing potential enrolling on study must have a negative serum pregnancy test prior to registration. * Childbearing potential is defined as women who are not postmenopausal (defined as amenorrheic for >= 12 months following cessation of any exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50; radiation-induced oophorectomy with last menses > 12 months prior; or chemotherapy-induced menopause with last menses > 12 months prior) or surgically sterile (bilateral oophorectomy or hysterectomy).
• Ability to understand and the willingness to sign a written informed consent document. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.

Exclusion Criteria

• Participants who have had chemotherapy, immune therapy, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C; five-half lives for any investigational or Food and Drug Administration [FDA]-approved kinase inhibitors) prior to entering the study. Patients who have received prior CHK1 inhibitor therapy are excluded. Exposure to prior PD-L1 antibody will be allowed as long as this was not the most recent treatment prior to enrollment.
• No prior radiation to > 25% of the marrow.
• Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.
• Participants who are receiving any other investigational agents.
• Participants who have undergone major surgery within 14 days of starting the study treatment, or participants who have not recovered to baseline status from the effects of major surgery received more than 14 days prior.
• Participants with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients with brain metastatic disease that has previously been treated and remained stable on MRI >= 2 months prior to enrollment, without steroids or anti-epileptic medications. These patients may be enrolled at the discretion of the principal investigator.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled seizures, myocardial infarction within the past 3 months, superior vena cava syndrome, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants must not have experienced a grade >= 3 immune-related adverse event (AE) or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy, or experienced a toxicity of any grade that led to permanent discontinuation of prior immunotherapy as a result of the toxicity. Participants with prior endocrine adverse events of grade =< 2 are permitted to enroll if stably maintained on appropriate replacement therapy and are asymptomatic. In the setting of prior immune-related AE, participants must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of the adverse event(s), not have experienced recurrence of the adverse event if re-challenged, and not currently requiring maintenance doses of > 10 mg of prednisone or equivalent per day at the time of enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to prexasertib or LY3300054.
• The effects of prexasertib and LY3300054 on the developing human fetus are unknown. For this reason, pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with prexasertib and LY3300054, breastfeeding women are also excluded.
• Known human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with prexasertib and LY3300054. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy such as prexasertib.
• Participants with known active or chronic infection with hepatitis B or C.
• Consistent corrected QT (QTc) > 470 msec on more than one screening electrocardiography (ECG). Patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded.