Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors
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).
- Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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.
- 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.
- Phase 2
- Study Type
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Combination A: Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck Combination B: Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will enroll participants with DDR defect positive mCRPC. Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
- Primary Purpose
- None (Open Label)
|Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck||
|Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.||
|Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC||
- Active, not recruiting
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