Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT04052204
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04052204
Recruitment Status : Not yet recruiting
First Posted : August 9, 2019
Last Update Posted : September 2, 2019
Sponsor:
Collaborators:
EMD Serono
Nektar Therapeutics
Astellas Pharma Inc
Information provided by (Responsible Party):
Pfizer

Brief 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).

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN) Metastatic Castration Resistant Prostate Cancer (mCRPC) Drug: avelumab Drug: Bempegaldesleukin Drug: talazoparib Drug: enzalutamide Phase 2

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


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
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

Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 29, 2019
Estimated Primary Completion Date : May 15, 2022
Estimated Study Completion Date : May 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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 Name: NKTR-214

Drug: talazoparib
poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
Other Name: 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 Name: NKTR-214

Drug: enzalutamide
androgen receptor inhibitor
Other Name: Xtandi




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1: Days 1-28 (28 days from the first dose of study treatment) ]
    Phase 1b: DLT during the DLT evaluation period (Cycle 1)

  2. Combination A: Confirmed objective response (OR) [ Time Frame: Baseline (C1D1) up to approximately 24 months. ]
    Phase 2: Confirmed OR, as assessed by the investigator using RECIST v1.1 in patients with SCCHN

  3. Combination B: Confirmed soft tissue OR [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    Phase 2: Confirmed OR, as assessed by the investigator, using RECIST v1.1 and PCWG3 criteria in patients with metastatic CRPC.

  4. Combination C: Confirmed prostate specific antigen (PSA) response [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    Phase 2: PSA response decrease ≥ 50% from baseline for patients with mCRPC.


Secondary Outcome Measures :
  1. Time to tumor response [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    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.

  2. Duration of tumor response [ Time Frame: Baseline (C1D1) up to approximately 24 months. ]
    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.

  3. Progression Free Survival (PFS) [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    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.

  4. Overall survival (OS) [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    OS is defined as the time from the first dose of study treatment to the date of death.

  5. Time to prostate-specific antigen (PSA) progression for mCRPC patients [ Time Frame: Baseline (C1D1) up to approximately 24 months ]
    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.

  6. 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) ]
    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.

  7. Biomarker PD-L1 [ Time Frame: Screening (SCCHN and mCRPC), Cycle 1 between Day 9 and Day 21 (SCCHN), or anytime on treatment (mCRPC) ]
    PD-L1 expression level in tumor tissue.

  8. Maximum serum concentration (Cmax) for avelumab [ Time Frame: Day 1, Day 15 of Cycles 1 and 2 (each cycle is 28 days) ]
    Cmax defined as the serum concentration of avelumab at EOI

  9. 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) ]
    Ctrough defined as the concentration of avelumab at the end of dosing interval.

  10. 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) ]
    Ctrough and Cmax defined as the concentration of bempegaldesleukin at the end of dosing interval and EOI, respectively.

  11. Trough plasma concentration for talazoparib [ Time Frame: Day 1 of Cycles 1, 2, 3 (each cycle is 28 days) ]
    Ctrough defined as the concentration of talazoparib at the end of dosing interval.

  12. 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) ]
    Ctrough defined as the concentration of enzalutamide and N-desmethyl-enzalutamide at the end of the dosing interval.

  13. 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) ]
    Immunogenicity assessment of avelumab

  14. 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) ]
    Immunogenicity assessment of bempegaldesleukin (NKTR-214) and IL-2.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04052204


Contacts
Layout table for location contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Layout table for location information
United States, Alaska
Alaska Clinical Research Center Not yet recruiting
Anchorage, Alaska, United States, 99503
United States, Florida
Precision Imaging Centers Not yet recruiting
Jacksonville Beach, Florida, United States, 32250
21st Century Oncology Not yet recruiting
Jacksonville, Florida, United States, 32204
21st Century Oncology Not yet recruiting
Jacksonville, Florida, United States, 32256
Sponsors and Collaborators
Pfizer
EMD Serono
Nektar Therapeutics
Astellas Pharma Inc
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04052204     History of Changes
Other Study ID Numbers: B9991040
2019-001358-24 ( EudraCT Number )
First Posted: August 9, 2019    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Squamous Cell Carcinoma of Head and Neck
Neoplasms by Site
Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Head and Neck Neoplasms
Talazoparib
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents