Clinical Trials /

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

NCT04052204

Description:

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).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1b/2 Study to Evaluate Safety and Clinical Activity of Avelumab in Combination With Bempegaldesleukin(NKTR-214) With or Without Talazoparib or Enzalutamide in Participants With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: B9991040
  • SECONDARY ID: 2019-001358-24
  • NCT ID: NCT04052204

Conditions

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

Interventions

DrugSynonymsArms
avelumabBavencio, MSB0010718CCombination A
BempegaldesleukinNKTR-214Combination A
talazoparibTalzennaCombination B
enzalutamideXtandiCombination C

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).

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
    

Trial Arms

NameTypeDescriptionInterventions
Combination AExperimentalAvelumab + 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
Combination BExperimentalAvelumab + 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.
  • avelumab
  • Bempegaldesleukin
  • talazoparib
Combination CExperimentalCombination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
  • avelumab
  • Bempegaldesleukin
  • enzalutamide

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; 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT)
Time Frame:Cycle 1: Days 1-28 (28 days from the first dose of study treatment)
Safety Issue:
Description:Phase 1b: DLT during the DLT evaluation period (Cycle 1)

Secondary Outcome Measures

Measure:Time to tumor response
Time Frame:Baseline (C1D1) up to approximately 24 months
Safety Issue:
Description:TTR is defined as the time from first dose to first documentation of objective tumor response (CR or PR). For participants whose objective response (OR) proceeds from PR to CR, the onset of PR is taken as the onset of response.
Measure:Duration of tumor response
Time Frame:Baseline (C1D1) up to approximately 24 months.
Safety Issue:
Description:Duration of Response (DR) is defined for patients with confirmed objective response(complete response [CR] or partial response [PR]) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression/death.
Measure:Progression Free Survival (PFS)
Time Frame:Baseline (C1D1) up to approximately 24 months
Safety Issue:
Description:Time from the date of first dose of study treatment to the date of the first documentation of PD/death due to any cause whichever occurs first.
Measure:Overall survival (OS)
Time Frame:Baseline (C1D1) up to approximately 24 months
Safety Issue:
Description:OS is defined as the time from the first dose of study treatment to the date of death.
Measure:Time to prostate-specific antigen (PSA) progression for mCRPC patients
Time Frame:Baseline (C1D1) up to approximately 24 months
Safety Issue:
Description:Time to PSA progression is defined as the time from the first dose to the date that a greater than or equal to 25% increase in PSA from baseline.
Measure:Circulating tumor cells (CTC) count and CTC0 for Combination C only patients
Time Frame:Screening, Baseline, Day 1 of Cycle 1, 3, 4 (each cycle is 28 days)
Safety Issue:
Description:CTC count conversion is defined as a decrease in CTC count from ≥ 5 CTC per 7.5 mL of blood at baseline to < 5 CTC per 7.5 mL of blood at any assessment on treatment. CTC0 is defined as a CTC count of ≥1 CTC per 7.5 mL of blood at baseline and 0 CTC per 7.5 mL of blood at any assessment on treatment.
Measure:Biomarker PD-L1
Time Frame:Screening (SCCHN and mCRPC), Cycle 1 between Day 9 and Day 21 (SCCHN), or anytime on treatment (mCRPC)
Safety Issue:
Description:PD-L1 expression level in tumor tissue.
Measure:Maximum serum concentration (Cmax) for avelumab
Time Frame:Day 1, Day 15 of Cycles 1 and 2 (each cycle is 28 days)
Safety Issue:
Description:Cmax defined as the serum concentration of avelumab at EOI
Measure:Trough serum concentration (Ctrough) of avelumab
Time Frame:Day 1, Day 15 of Cycles 1 and 2; Day 1 of Cycles 3,6, 9 and 12 (each cycle is 28 days)
Safety Issue:
Description:Ctrough defined as the concentration of avelumab at the end of dosing interval.
Measure:Trough and maximum plasma concentration of bempegaldesleukin (NKTR-214)
Time Frame:Day 1, Day 3, Day 4, Day 8 of Cycle 1; Day 1 and Day 8 of Cycle 2; Day 1 Cycles 3,6, 9 and 12 (each cycle is 28 days)
Safety Issue:
Description:Ctrough and Cmax defined as the concentration of bempegaldesleukin at the end of dosing interval and EOI, respectively.
Measure:Trough plasma concentration for talazoparib
Time Frame:Day 1 of Cycles 1, 2, 3 (each cycle is 28 days)
Safety Issue:
Description:Ctrough defined as the concentration of talazoparib at the end of dosing interval.
Measure:Trough plasma concentration Ctrough for enzalutamide and N-desmethyl-enzalutamide
Time Frame:Day 1 of Cycles 1, 2, 3, and 6 (each cycle is 28 days)
Safety Issue:
Description:Ctrough defined as the concentration of enzalutamide and N-desmethyl-enzalutamide at the end of the dosing interval.
Measure:Incidence of Anti-drug antibody (ADA) and neutralizing antibodies (NAb) against avelumab
Time Frame:Day 1 of Cycles 1, 2, 3, 6, 9, 12 and EOT (each cycle is 28 days)
Safety Issue:
Description:Immunogenicity assessment of avelumab
Measure:Incidence of Anti-drug antibody (ADA) and neutralizing antibodies (NAb) against bempegaldesleukin (NKTR-214) and IL-2
Time Frame:Day 1 of Cycles 1, 2, 3, 6, 9, 12 and EOT (each cycle is 28 days)
Safety Issue:
Description:Immunogenicity assessment of bempegaldesleukin (NKTR-214) and IL-2.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Last Updated