avelumab with bempegaldesleukin with or without talazoparib or enzalutamide in advanced or metastatic solid tumors

Conditions: Squamous Cell Carcinoma of the Head and Neck (SCCHN); Metastatic Castration Resistant Prostate Cancer (mCRPC)

Summary: evaluation of the combination of avelumab + bempegaldesleukin (nktr-214 ) in locally advanced squamous cell carcinoma of the head and neck ( metastatic scchn) and avelumab + bempegaldesleukin (nktr-214) + talazoparib or enzalutamide in metastatic castration resistant prostate cancer (mcrpc).

phase 1b/ phase 2 design phase 1b will be the sequential dose-finding study. once the phase 1b component is completed, phase 2 will be initiated to further evaluate the safety and anti-tumor activity across combinations of therapy. combination a will enroll participants with scchn. combination b and c will enroll participants with mcrpc

Eligibility criteria:
inclusion criteria: * participants must be ≥ 18 years old. * participants with scchn or mcrcp. * participants must have histological diagnosis of solid tumors and provide tumor tissue. * measurable disease by recist v1.1 with at least 1 measurable lesion. * eastern cooperative oncology group (ecog) performance status (ps) 0 or 1. * adequate bone marrow, renal and liver function * highly effective contraceptive use by men with the ability to father a child or women of childbearing potential. * a wocbp must have a negative highly sensitive pregnancy test (\[urine or serum\] as required by local regulations) at c1d1. * signed and dated informed consent. exclusion criteria: * known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monocolonal antibodies. * known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis. * active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. * prior organ transplantation including allogenic stem cell transplantation. * vaccination within 4 weeks prior to c1d1 and while on trial is prohibited except for administration of inactivated vaccines. * known symptomatic brain lesions requiring steroids. * known history of testing positive for human immunodeficiency virus (hiv or known acquired immunodeficiency syndrome (aids). * positive hbv surface antigen or hcv test indicating acute or chronic infection.. * active infection requiring systemic therapy * clinically significant (i.e., active) cardiovascular disease including the following: documented left ventricular ejection fraction (lvef) \<50% by echo/muga; cerebral vascular accident/stroke or transient ischemic attack; myocardial infarction; unstable angina; congestive heart failure or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication. * diagnosis of any other malignancy within 2 years prior to c1d1, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix and for combination a only, low-grade (gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration) or adequately treated prostate cancer. * current use of immunosuppressive medication at the time of study enrollment. * major surgery within 4 weeks prior to study enrollment. * conditions that may impair intake or absorption such as inability to swallow capsules or tablets; known malabsorption syndrome; or baseline diarrhea ≤ grade 1. * participation in other studies involving investigational drug(s) within 2 weeks prior to c1d1.