Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

Purpose

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).

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
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
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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
  • Drug: avelumab
    Investigational fully human anti-PD-L1 monoclonal antibody
    Other names:
    • Bavencio
    • MSB0010718C
  • Drug: Bempegaldesleukin
    Investigational CD122-biased cytokine agonist
    Other names:
    • NKTR-214
Experimental
Combination B 		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.
  • Drug: avelumab
    Investigational fully human anti-PD-L1 monoclonal antibody
    Other names:
    • Bavencio
    • MSB0010718C
  • Drug: Bempegaldesleukin
    Investigational CD122-biased cytokine agonist
    Other names:
    • NKTR-214
  • Drug: talazoparib
    poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
    Other names:
    • Talzenna
Experimental
Combination C 		Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
  • Drug: avelumab
    Investigational fully human anti-PD-L1 monoclonal antibody
    Other names:
    • Bavencio
    • MSB0010718C
  • Drug: Bempegaldesleukin
    Investigational CD122-biased cytokine agonist
    Other names:
    • NKTR-214
  • Drug: enzalutamide
    androgen receptor inhibitor
    Other names:
    • Xtandi

More Details

Status
Terminated
Sponsor
Pfizer

Study Contact

Detailed Description

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