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QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy

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. Read our disclaimer for details. Identifier: NCT03853317
Recruitment Status : Terminated (Not meeting recruitment goal)
First Posted : February 25, 2019
Last Update Posted : January 11, 2022
Information provided by (Responsible Party):
ImmunityBio, Inc.

Brief Summary:
Phase 2, single-arm study to evaluate combination therapy of avelumab, haNK and N-803 in patients with Merkel Cell Carcinoma who have progressed on or after checkpoint inhibitor therapy as assessed by ORR. Patients will receive treatment for a maximum of two years.

Condition or disease Intervention/treatment Phase
Merkel Cell Carcinoma Biological: Avelumab Biological: N-803 Biological: haNK™ Phase 2

Detailed Description:
This is a phase II, single-arm study of combination therapy of avelumab, haNK, and N-803 in patients with Merkel Cell Carcinoma who have progressed on or after checkpoint inhibitor therapy as assessed by ORR. Patients must have progressed on or within six months of completing treatment with either avelumab or pembrolizumab. Patients will received treatment for a maximum of two years, with avelumab and haNK administered every two weeks, and N-803 administered every three weeks. Radiologic evaluation will occur every eight weeks during the first year of treatment, and every twelve weeks during the second year of treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: QUILT-3.063: A Phase 2 Study of Combination Therapy With an IL-15 Superagonist (N-803), Off-the-shelf CD16-targeted Natural Killer Cells (haNK), and Avelumab Without Cytotoxic Chemotherapy in Subjects With Merkel Cell Carcinoma (MCC) That Has Progressed on or After Treatment With a Checkpoint Inhibitor.
Actual Study Start Date : February 24, 2020
Actual Primary Completion Date : October 1, 2021
Actual Study Completion Date : October 1, 2021

Arm Intervention/treatment
Experimental: Treatment with avelumab, haNK™ and N-803
The primary objective is to determine the efficacy of the combination treatment of avelumab, haNK, and N-803 in subjects with MCC that has progressed on or after checkpoint inhibitor therapy by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on Blinded Independent Central Review (BICR).
Biological: Avelumab
For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).
Other Name: (BAVENCIO® injection, for intravenous [IV] use)

Biological: N-803
Recombinant human super agonist interleukin-15 (IL-15) complex
Other Name: also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803

Biological: haNK™
haNK™ for Infusion is a human, allogeneic, NK cell line that has been engineered to produce endogenous, intracellularly retained IL-2 and to express CD16, the high-affinity (158V) Fc gamma receptor (FcγRIIIa/CD16a).
Other Name: NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 24 Months ]
    Defined by RECIST 1.1 based on BICR.

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 based on BICR.

  2. Duration of Response (DOR) [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 based on BICR.

  3. PFS [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 and irRECIST based on BICR.

  4. Overall Survival (OS) [ Time Frame: 24 Months ]
    Graded using CTCAE Version 5.0.

  5. Disease-Specific Survival (DSS) [ Time Frame: 24 Months ]
    Analyzed using Kaplan-Meier Methods.

  6. Disease Control Rate (DCR) [ Time Frame: 2 Months ]
    Confirmed CR, PR, or stable disease [SD] lasting for greater than 2 months, by RECIST Version 1.1 and irRECIST by BICR.

  7. Quality of Life Questionnaire [ Time Frame: 24 Months ]
    Conducted via PROs using the Functional Assessment of Cancer Therapy-Melanoma (FACT-M)

Other Outcome Measures:
  1. Incidence of treatment-emergent AEs and SAEs [ Time Frame: 24 Months ]
    Graded using the NCI CTCAE Version 5.0

  2. Immunogenicity profile of N-803 in combination with avelumab and haNK [ Time Frame: 24 Months ]
    Detection of anti-drug antibodies.

  3. Pharmacokinetic profile of N-803 in combination with avelumab and haNK [ Time Frame: 24 Months ]
    Maximum observed concentration (Cmax)

  4. Tumor molecular profiles and correlations with subject outcomes [ Time Frame: 9 weeks ]
    Genomic sequencing of tumor cells from tissue.

  5. Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. [ Time Frame: 24 Months. ]
    Expression levels of specific tumor- and immune-related analytes in ctDNA and ctRNA will be measured by qPCR

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.

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

Inclusion Criteria:

  1. Age ≥ 18 years on day of signing informed consent.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
  3. Histologically-confirmed metastatic MCC that has progressed during treatment or within 6 months after completing treatment with single-agent avelumab or pembrolizumab therapy, as per FDA indication.
  4. ECOG performance status of 0 to 2.
  5. Have at least 1 measurable lesion of ≥ 1.0 cm.
  6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen for exploratory tumor molecular profiling. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
  7. Must be willing to provide blood samples for exploratory analyses.
  8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
  9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  10. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria:

  1. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
  2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, [subjects with mild rheumatoid arthritis that aren't currently receiving treatment for their disease are eligible for enrollment], Addison's disease, or autoimmune disease associated with lymphoma).
  3. History of organ transplant requiring immunosuppression.
  4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  5. Inadequate organ function, evidenced by the following laboratory results:

    1. ANC < 900 cells/mm3.
    2. Platelet count < 75,000 cells/mm3
    3. Total bilirubin greater than twice the ULN (unless the subject has documented Gilbert's syndrome).
    4. AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    5. ALP levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
  6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
  7. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  8. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
  9. Known hypersensitivity to any component of the study medication(s), including anaphylactic reaction to sulfur-containing medications.
  10. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  11. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to the start of treatment on this study, except for testosterone-lowering therapy in men with prostate cancer.
  12. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  13. Concurrent participation in any interventional clinical trial.
  14. Pregnant and nursing women.

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 identifier (NCT number): NCT03853317

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United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Miami Cancer Institute - Baptist Health
Miami, Florida, United States, 33176
United States, Missouri
Washington University School of Medicine in St. Louis
Saint Louis, Missouri, United States, 63110
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
ImmunityBio, Inc.
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Study Director: Lennie Sender, MD ImmunityBio, Inc.
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Responsible Party: ImmunityBio, Inc. Identifier: NCT03853317    
Other Study ID Numbers: QUILT-3.063
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: January 11, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Antineoplastic Agents, Immunological
Antineoplastic Agents