Clinical Trials /

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

NCT03853317

Description:

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.

Related Conditions:
  • Merkel Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.063
  • NCT ID: NCT03853317

Conditions

  • Merkel Cell Carcinoma

Interventions

DrugSynonymsArms
Avelumab(BAVENCIO® injection, for intravenous [IV] use)Treatment with avelumab, haNK™ and N-803
N-803also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803Treatment with avelumab, haNK™ and N-803
haNKNK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)Treatment with avelumab, haNK™ and N-803

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment with avelumab, haNK™ and N-803ExperimentalThe 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).
  • Avelumab
  • N-803
  • haNK

Eligibility Criteria

        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 prior to the start of treatment on this study
             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, 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. Positive results of screening test for HIV.

          9. 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.

         10. Known hypersensitivity to any component of the study medication(s).

         11. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
             reaction with any of the study medications.

         12. Participation in an investigational drug study or history of receiving any
             investigational treatment within 14 days prior to screening for this study, except for
             testosterone-lowering therapy in men with prostate cancer.

         13. Assessed by the Investigator to be unable or unwilling to comply with the requirements
             of the protocol.

         14. Concurrent participation in any interventional clinical trial.

         15. Pregnant and nursing women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST 1.1 based on BICR.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR.
Measure:Duration of Response (DOR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR.
Measure:PFS
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 and irRECIST based on BICR.
Measure:Overall Survival (OS)
Time Frame:24 Months
Safety Issue:
Description:Graded using CTCAE Version 5.0.
Measure:Disease-Specific Survival (DSS)
Time Frame:24 Months
Safety Issue:
Description:Analyzed using Kaplan-Meier Methods.
Measure:Disease Control Rate (DCR)
Time Frame:2 Months
Safety Issue:
Description:Confirmed CR, PR, or stable disease [SD] lasting for greater than 2 months, by RECIST Version 1.1 and irRECIST by BICR.
Measure:Quality of Life Questionnaire
Time Frame:24 Months
Safety Issue:
Description:Conducted via PROs using the Functional Assessment of Cancer Therapy-Melanoma (FACT-M)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NantKwest, Inc.

Last Updated

March 18, 2020