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

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 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
Active, not recruiting
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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.