Merkel Cell Carcinoma
Conditions
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.
Interventions
BIOLOGICALAvelumab
For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).
BIOLOGICALN-803
Recombinant human super agonist interleukin-15 (IL-15) complex
BIOLOGICALhaNK™
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).
Sponsors
ImmunityBio, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 2 years | Overall Survival defined as the time from the date of first treatment to death by any cause |
| Disease-Specific Survival | Up to 2 years | Disease-Specific Survival defined as the time from the date of first treatment to death resulting from MCC |
| Overall Response Rate by iRECIST (Percent of Subjects With Confirmed Complete or Partial Overall Response) | Up to 2 years | 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 |
| FACT-M Total Score | Baseline, Week 13, and End of Treatment visit, up to 2 years | 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 |
| Duration of Response by RECIST Version 1.1 and iRECIST | From time of CR or PR up to 2 years | 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. |
| Disease Control Rate | Up to 2 years | 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 |
| Progression Free Survival | Up to 2 years | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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)
Avelumab: For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).
N-803: Recombinant human super agonist interleukin-15 (IL-15) complex
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). | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | other event | 2 |
| Overall Study | Progressive Disease | 5 |
Baseline characteristics
| Characteristic | Treatment With Avelumab, haNK™ and N-803 |
|---|---|
| Age, Continuous | 71.4 years STANDARD_DEVIATION 8.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Histologically-confirmed metastatic MCC that has progressed during treatment or within 6 months | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 5 / 9 |
Outcome results
Primary
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
Time frame: 30 days after last dose, approximately 1 year 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Number of Participants With Adverse Events | 9 Participants |
Primary
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
Time frame: approximately 1 year 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Objective Response Rate | 0 Percent of Subjects |
Secondary
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
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Disease Control Rate | 0 Percent of Subjects |
Secondary
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
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Disease Control Rate | 0.00 Percent of Subjects |
Secondary
Disease-Specific Survival
Disease-Specific Survival defined as the time from the date of first treatment to death resulting from MCC
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Disease-Specific Survival | NA months |
Secondary
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.
Time frame: From time of CR or PR up to 2 years
Population: No subject had a complete or partial response
Secondary
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
Time frame: Baseline, Week 13, and End of Treatment visit, up to 2 years
Population: At week 13 only 2 subjects had quality of life measurements. At end of treatment only 5 subjects had quality of life measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | FACT-M Total Score | Baseline | 143.8 Scores on a scale | Standard Deviation 26.55 |
| Treatment With Avelumab, haNK™ and N-803 | FACT-M Total Score | Week 13 | 144.5 Scores on a scale | Standard Deviation 13.44 |
| Treatment With Avelumab, haNK™ and N-803 | FACT-M Total Score | End of Treatment | 126.6 Scores on a scale | Standard Deviation 31.55 |
Secondary
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
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Overall Response Rate by iRECIST (Percent of Subjects With Confirmed Complete or Partial Overall Response) | 0 Percent of Subjects |
Secondary
Overall Survival
Overall Survival defined as the time from the date of first treatment to death by any cause
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Overall Survival | 5.6 months |
Secondary
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
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Progression Free Survival | 1.9 Months |
Secondary
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
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment With Avelumab, haNK™ and N-803 | Progression Free Survival | 1.9 months |