QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy
Primary Purpose
Merkel Cell Carcinoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Avelumab
N-803
haNK™
Sponsored by
About this trial
This is an interventional treatment trial for Merkel Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years on day of signing informed consent.
- Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
- 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.
- ECOG performance status of 0 to 2.
- Have at least 1 measurable lesion of ≥ 1.0 cm.
- 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.
- Must be willing to provide blood samples for exploratory analyses.
- 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.
- Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
- 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:
- 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.
- 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).
- History of organ transplant requiring immunosuppression.
- History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
Inadequate organ function, evidenced by the following laboratory results:
- ANC < 900 cells/mm3.
- Platelet count < 75,000 cells/mm3
- Total bilirubin greater than twice the ULN (unless the subject has documented Gilbert's syndrome).
- AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
- ALP levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
- 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.
- Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
- 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.
- Known hypersensitivity to any component of the study medication(s), including anaphylactic reaction to sulfur-containing medications.
- Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
- 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.
- Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
- Concurrent participation in any interventional clinical trial.
- Pregnant and nursing women.
Sites / Locations
- University of California San Francisco
- University of Miami, Sylvester Comprehensive Cancer Center
- Miami Cancer Institute - Baptist Health
- Washington University School of Medicine in St. Louis
- Cleveland Clinic Foundation
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment with avelumab, haNK™ and N-803
Arm Description
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).
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR)
Defined by RECIST 1.1 based on BICR.
Secondary Outcome Measures
Overall Response Rate (ORR)
Defined by RECIST Version 1.1 based on BICR.
Duration of Response (DOR)
Defined by RECIST Version 1.1 based on BICR.
PFS
Defined by RECIST Version 1.1 and irRECIST based on BICR.
Overall Survival (OS)
Graded using CTCAE Version 5.0.
Disease-Specific Survival (DSS)
Analyzed using Kaplan-Meier Methods.
Disease Control Rate (DCR)
Confirmed CR, PR, or stable disease [SD] lasting for greater than 2 months, by RECIST Version 1.1 and irRECIST by BICR.
Quality of Life Questionnaire
Conducted via PROs using the Functional Assessment of Cancer Therapy-Melanoma (FACT-M)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03853317
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Not meeting recruitment goal
Study Start Date
February 24, 2020 (Actual)
Primary Completion Date
October 1, 2021 (Actual)
Study Completion Date
October 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ImmunityBio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Merkel Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment with avelumab, haNK™ and N-803
Arm Type
Experimental
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
Avelumab
Other Intervention Name(s)
(BAVENCIO® injection, for intravenous [IV] use)
Intervention Description
For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).
Intervention Type
Biological
Intervention Name(s)
N-803
Other Intervention Name(s)
also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803
Intervention Description
Recombinant human super agonist interleukin-15 (IL-15) complex
Intervention Type
Biological
Intervention Name(s)
haNK™
Other Intervention Name(s)
NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Defined by RECIST 1.1 based on BICR.
Time Frame
24 Months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Defined by RECIST Version 1.1 based on BICR.
Time Frame
24 Months
Title
Duration of Response (DOR)
Description
Defined by RECIST Version 1.1 based on BICR.
Time Frame
24 Months
Title
PFS
Description
Defined by RECIST Version 1.1 and irRECIST based on BICR.
Time Frame
24 Months
Title
Overall Survival (OS)
Description
Graded using CTCAE Version 5.0.
Time Frame
24 Months
Title
Disease-Specific Survival (DSS)
Description
Analyzed using Kaplan-Meier Methods.
Time Frame
24 Months
Title
Disease Control Rate (DCR)
Description
Confirmed CR, PR, or stable disease [SD] lasting for greater than 2 months, by RECIST Version 1.1 and irRECIST by BICR.
Time Frame
2 Months
Title
Quality of Life Questionnaire
Description
Conducted via PROs using the Functional Assessment of Cancer Therapy-Melanoma (FACT-M)
Time Frame
24 Months
Other Pre-specified Outcome Measures:
Title
Incidence of treatment-emergent AEs and SAEs
Description
Graded using the NCI CTCAE Version 5.0
Time Frame
24 Months
Title
Immunogenicity profile of N-803 in combination with avelumab and haNK
Description
Detection of anti-drug antibodies.
Time Frame
24 Months
Title
Pharmacokinetic profile of N-803 in combination with avelumab and haNK
Description
Maximum observed concentration (Cmax)
Time Frame
24 Months
Title
Tumor molecular profiles and correlations with subject outcomes
Description
Genomic sequencing of tumor cells from tissue.
Time Frame
9 weeks
Title
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes.
Description
Expression levels of specific tumor- and immune-related analytes in ctDNA and ctRNA will be measured by qPCR
Time Frame
24 Months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years on day of signing informed consent.
Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
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.
ECOG performance status of 0 to 2.
Have at least 1 measurable lesion of ≥ 1.0 cm.
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.
Must be willing to provide blood samples for exploratory analyses.
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.
Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
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:
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.
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).
History of organ transplant requiring immunosuppression.
History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
Inadequate organ function, evidenced by the following laboratory results:
ANC < 900 cells/mm3.
Platelet count < 75,000 cells/mm3
Total bilirubin greater than twice the ULN (unless the subject has documented Gilbert's syndrome).
AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
ALP levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
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.
Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
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.
Known hypersensitivity to any component of the study medication(s), including anaphylactic reaction to sulfur-containing medications.
Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
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.
Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
Concurrent participation in any interventional clinical trial.
Pregnant and nursing women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bobby Reddy, MD
Organizational Affiliation
ImmunityBio, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Miami, Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Miami Cancer Institute - Baptist Health
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Washington University School of Medicine in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Learn more about this trial
QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy
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