Merkel Cell CarcinomaPhase 2NCT03853317
QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy
A Phase 2 study testing Avelumab, N-803 and haNK™ in people with Merkel Cell Carcinoma, run by ImmunityBio, Inc. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma
- What is being tested?
- Avelumab, N-803 and haNK™
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 5 sitesUnited States
- Study dates
- 19 Feb 2020to 19 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Miami Cancer Institute - Baptist Health
Miami, Florida, 33176
University of California San Francisco
San Francisco, California, 94143
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
About this study
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.
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.
Read the 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.
- Conditions
- Merkel Cell Carcinoma
- Being tested
- Avelumab, N-803, haNK™
- Medical subject headings
- Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabBiological
Also called (BAVENCIO® injection, for intravenous [IV] use)
For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).
N-803Biological
Also called also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803
Recombinant human super agonist interleukin-15 (IL-15) complex
haNK™Biological
Also called NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)
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).
| Study group | Role | What they receive |
|---|---|---|
| Treatment with avelumab, haNK™ and N-803 | Experimental | 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) Receives: Biological: Avelumab; Biological: N-803; Biological: haNK™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: approximately 1 year 7 months
Secondary outcomes (9)
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
Measured: 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
Measured: 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
Measured: Up to 2 years
Overall Survival
Overall Survival defined as the time from the date of first treatment to death by any cause
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: From time of CR or PR up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2019
- Study start19 Feb 2020
- Primary completion29 Sep 2021
- Study completion19 Sep 2022
Why it stopped: Not meeting recruitment goal
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by ImmunityBio, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunityBio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bobby Reddy, MD, Study director, ImmunityBio, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03853317
- Sponsor's protocol ID
- QUILT-3.063
- Status last verified
- Aug 2024
- First submitted
- 14 Feb 2019
- Last updated
- 9 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03853317
- Acronym / sponsor ID
- QUILT-3.063
- Conditions
- Merkel Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not meeting recruitment goal
- Enrolment
- 9 participants (actual)
- Lead sponsor
- ImmunityBio, Inc.Industry (pharma, biotech, devices)
- Study start
- 19 Feb 2020 (actual)
- Primary completion
- 29 Sep 2021 (actual)
- Study completion
- 19 Sep 2022 (actual)
- First posted
- 25 Feb 2019 (actual)
- Results
- Posted 9 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with avelumab, haNK™ and N-803 | Experimental | Biological: Avelumab, Biological: N-803, Biological: haNK™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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAlso: (BAVENCIO® injection, for intravenous [IV] use)For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC). | Biological | Treatment with avelumab, haNK™ and N-803 |
| N-803Also: also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803Recombinant human super agonist interleukin-15 (IL-15) complex | Biological | Treatment with avelumab, haNK™ and N-803 |
| haNK™Also: NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)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). | Biological | Treatment with avelumab, haNK™ and N-803 |
Primary outcome
Number of Participants With Adverse Events
Time frame: 30 days after last dose, approximately 1 year 7 months
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
Objective Response Rate
Time frame: approximately 1 year 7 months
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
9 secondary outcomes
Overall Response Rate by iRECIST (Percent of Subjects With Confirmed Complete or Partial Overall Response)
Time frame: Up to 2 years
Progression Free Survival
Time frame: Up to 2 years
Progression Free Survival
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 2 years
Disease-Specific Survival
Time frame: Up to 2 years
Disease Control Rate
Time frame: Up to 2 years
Disease Control Rate
Time frame: Up to 2 years
FACT-M Total Score
Time frame: Baseline, Week 13, and End of Treatment visit, up to 2 years
Duration of Response by RECIST Version 1.1 and iRECIST
Time frame: From time of CR or PR up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bobby Reddy, MD study director
ImmunityBio, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab, N-803 and haNK™ in people with Merkel Cell Carcinoma, run by ImmunityBio, Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: 30 days after last dose, approximately 1 year 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.