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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Merkel Cell Carcinoma
• Intervention / Treatment: Biological: Avelumab; Biological: N-803; Biological: haNK™

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute - Baptist Health
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

Biological: Avelumab; For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).; Other Names: (BAVENCIO® injection, for intravenous [IV] use); Biological: N-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Other Names: 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 Names: NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	The safety of the combination treatment of avelumab, haNK, and N-803 in subjects with MCC that has progressed on or after checkpoint inhibitor therapy	30 days after last dose, approximately 1 year 7 months
Objective Response Rate	Percent of subjects with confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1	approximately 1 year 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate by iRECIST (Percent of Subjects With Confirmed Complete or Partial Overall Response)	Percent of subjects with confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions) by iRECIST	Up to 2 years
Progression Free Survival	Defined as the time from the date of first treatment to disease progression or death by any cause, whichever occurs first by RECIST v1.1	Up to 2 years
Progression Free Survival	Defined as the time from the date of first treatment to disease progression or death by any cause, whichever occurs first by iRECIST	Up to 2 years
Overall Survival	Overall Survival defined as the time from the date of first treatment to death by any cause	Up to 2 years
Disease-Specific Survival	Disease-Specific Survival defined as the time from the date of first treatment to death resulting from MCC	Up to 2 years
Disease Control Rate	Percent of subjects with stable disease for >= 8 weeks, or confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1	Up to 2 years
Disease Control Rate	Percent of subjects with stable disease for >= 8 weeks, or confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions) by iRECIST	Up to 2 years
FACT-M Total Score	Quality of Life Measures as measured by the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) instrument's FACT-M Total Score. The FACT-M total score is a sum of the questions from its six subscales (a sum of 51 questions in total): Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Additional Concerns, and At the Site of Melanoma. All subscale questions use a 5-point Likert-type response score ranging from 0 = 'not at all' to 4 = 'very much'. The FACT-M Total score, therefore, ranges from 0 to 204. Negatively worded items are reverse scored prior to summing so that higher subscale and total scores indicate a better quality of life	Baseline, Week 13, and End of Treatment visit, up to 2 years
Duration of Response by RECIST Version 1.1 and iRECIST	Duration of Response is defined as the time from the date of first response (Investigator-assessed PR or CR) to the date of disease progression or death (any cause) whichever occurs first. Per RECIST and iRECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From time of CR or PR up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent AEs and SAEs	Graded using the NCI CTCAE Version 5.0	24 Months
Immunogenicity profile of N-803 in combination with avelumab and haNK	Detection of anti-drug antibodies.	24 Months
Pharmacokinetic profile of N-803 in combination with avelumab and haNK	Maximum observed concentration (Cmax)	24 Months
Tumor molecular profiles and correlations with subject outcomes	Genomic sequencing of tumor cells from tissue.	9 weeks
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes.	Expression levels of specific tumor- and immune-related analytes in ctDNA and ctRNA will be measured by qPCR	24 Months.

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.
• Investigators: Study Director: Bobby Reddy, MD, ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): September 29, 2021
• Study Completion (Actual): September 19, 2022

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma; Carcinoma, Merkel Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: QUILT-3.063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No