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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avelumab | Biological | For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC). |
|
| 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 |
| 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 |
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Inclusion Criteria:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Bobby Reddy, MD | ImmunityBio, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | San Francisco | California | 94143 | United States | ||
| University of Miami, Sylvester Comprehensive Cancer Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 17, 2021 |
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|
| N-803 | Biological | Recombinant human super agonist interleukin-15 (IL-15) complex |
|
|
| haNK™ | Biological | 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). |
|
|
| 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 |
| Miami |
| Florida |
| 33136 |
| United States |
| Miami Cancer Institute - Baptist Health | Miami | Florida | 33176 | United States |
| Washington University School of Medicine in St. Louis | St Louis | Missouri | 63110 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Histologically-confirmed metastatic MCC that has progressed during treatment or within 6 months | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 30 days after last dose, approximately 1 year 7 months |
|
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| |||||||||||||||||||||||||||
| 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 | Posted | Number | 95% Confidence Interval | Percent of Subjects | approximately 1 year 7 months |
|
| |||||||||||||||||||||||||||
| 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 | Posted | Number | 95% Confidence Interval | Percent of Subjects | Up to 2 years |
|
| |||||||||||||||||||||||||||
| 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 | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
| |||||||||||||||||||||||||||
| 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 | Posted | Median | 95% Confidence Interval | Months | Up to 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall Survival defined as the time from the date of first treatment to death by any cause | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | Disease-Specific Survival | Disease-Specific Survival defined as the time from the date of first treatment to death resulting from MCC | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
| |||||||||||||||||||||||||||
| 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 | Posted | Number | 95% Confidence Interval | Percent of Subjects | Up to 2 years |
|
| |||||||||||||||||||||||||||
| 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 | Posted | Number | 95% Confidence Interval | Percent of Subjects | Up to 2 years |
|
| |||||||||||||||||||||||||||
| 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 | At week 13 only 2 subjects had quality of life measurements. At end of treatment only 5 subjects had quality of life measurements. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Week 13, and End of Treatment visit, up to 2 years |
| |||||||||||||||||||||||||||
| 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. | No subject had a complete or partial response | Posted | From time of CR or PR up to 2 years |
|
|
30 days after last dose, up to 2 years or until resolution or stabilization for nonserious grade 3 or 4 AEs and SAEs, whichever is longer.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 4 | 9 | 5 | 9 | 9 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Oedema peripheral | General disorders | Systematic Assessment |
| ||
| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Haematuria | Renal and urinary disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chills | General disorders | Systematic Assessment |
| ||
| pyrexia | General disorders | Systematic Assessment |
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| fatigue | General disorders | Systematic Assessment |
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| Injection site erythrma | General disorders | Systematic Assessment |
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| Injection site pruritus | General disorders | Systematic Assessment |
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| Injection site reaction | General disorders | Systematic Assessment |
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| asthenia | General disorders | Systematic Assessment |
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| Chest discomfort | General disorders | Systematic Assessment |
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| Oedema peripheral | General disorders | Systematic Assessment |
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| Pain | General disorders | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Eosinophilia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Blood creatinine increased | Investigations | Systematic Assessment |
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| Blood lactate dehydrogenase | Investigations | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Weight decreased | Investigations | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | Systematic Assessment |
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| Glycosuria | Renal and urinary disorders | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
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| Wound complication | Injury, poisoning and procedural complications | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Candida infection | Infections and infestations | Systematic Assessment |
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| Fungal infection | Infections and infestations | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash maculo-papular | Vascular disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Lymphoedema | Vascular disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandeep Bobby Reddy, Chief Medical Officer | ImmunityBio | 855-797-9277 | Bobby.Reddy@immunitybio.com |
| Apr 3, 2024 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015266 | Carcinoma, Merkel Cell |
| ID | Term |
|---|---|
| D027601 | Polyomavirus Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D018278 | Carcinoma, Neuroendocrine |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| C000609138 | avelumab |
| C582303 | ALT-803 |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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