QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy
Primary Purpose
Merkel Cell Carcinoma
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Avelumab
Bevacizumab
Capecitabine
Cisplatin
Cyclophosphamide
5-fluorouracil
Leucovorin
nab-Paclitaxel
omega-3-acid ethyl esters
Stereotactic Body Radiation Therapy
ALT-803
ETBX-051
ETBX-061
GI-6301
haNK
Sponsored by
About this trial
This is an interventional treatment trial for Merkel Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years.
- Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
- Histologically-confirmed metastatic or unresectable MCC with progression on or after anti-PD-L1 therapy (eg, avelumab).
- ECOG performance status of 0 to 2.
- Have at least 1 measurable lesion of ≥ 1.5 cm.
- Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anti-cancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
- Must be willing to provide blood samples for exploratory analyses, and if considered safe by the investigator, a tumor biopsy specimen at 8 weeks after the start of treatment.
- 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.
Exclusion Criteria:
- History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
- History of other active malignancies or brain metastasis except: controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable PSA (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. Subjects with a history of another malignancy must have > 5 years without evidence of disease.
- 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, Addison's disease, autoimmune disease associated with lymphoma).
- History of organ transplant requiring immunosuppression.
- History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
- Requires whole blood transfusion to meet eligibility criteria.
Inadequate organ function, evidenced by the following laboratory results:
- WBC count < 3,500 cells/mm3.
- Absolute neutrophil count < 1,500 cells/mm3.
- Platelet count < 100,000 cells/mm3.
- Hemoglobin < 9 g/dL.
- Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
- AST (SGOT)) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
- Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
- Serum creatinine > 2.0 mg/dL or 177 μmol/L.
- INR or aPTT or PTT >1.5 × ULN (unless on therapeutic anti-coagulation).
- Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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.
- Positive results of screening test for HIV, HBV, or HCV.
- 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).
- Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
- Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
- Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
- Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for 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
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NANT MCC Vaccine
Arm Description
A combination of agents will be administered to subjects in this study: avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, stereotactic body radiation therapy, ALT-803, ETBX-051, ETBX-061, GI-6301, and haNK.
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Phase 1b primary endpoint
Objective response rate by RECIST Version 1.1
Phase 2 primary endpoint
Objective response rate by irRC
Phase 2 primary endpoint
Secondary Outcome Measures
Objective response rate by RECIST Version 1.1
Phase 1b secondary endpoint
Objective response rate by irRC
Phase 1b secondary endpoint
Progression-free survival by RECIST Version 1.1
Phase 1b and Phase 2 secondary endpoint
Progression-free survival by irRC
Phase 1b and Phase 2 secondary endpoint
Overall survival
Phase 1b and Phase 2 secondary endpoint
Duration of response
Phase 1b and Phase 2 secondary endpoint
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months)
Phase 1b and Phase 2 secondary endpoint
Quality of life by patient-reported outcome using Functional Assessment of Cancer Therapy-Melanoma (FACT-M) Questionnaire
Phase 1b and Phase 2 secondary endpoint
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
Phase 2 secondary endpoint
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03167164
Brief Title
QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy
Official Title
NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After Anti-programmed Death-ligand 1 (PD-L1) Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Trial not initiated
Study Start Date
December 2017 (Anticipated)
Primary Completion Date
January 2019 (Anticipated)
Study Completion Date
March 2019 (Anticipated)
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
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with MCC who have progressed on or after anti-PD-L1 therapy.
Detailed Description
Treatment will be administered in two phases. Subjects will continue treatment until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) will enter phase 2 of the study. Subjects may remain on phase 2 of the study for up to 1 year. Treatment will continue in phase 2 until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the investigator feels it is no longer in the subject's best interest to continue 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 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NANT MCC Vaccine
Arm Type
Experimental
Arm Description
A combination of agents will be administered to subjects in this study:
avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, stereotactic body radiation therapy, ALT-803, ETBX-051, ETBX-061, GI-6301, and haNK.
Intervention Type
Biological
Intervention Name(s)
Avelumab
Intervention Description
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
Intervention Type
Biological
Intervention Name(s)
Bevacizumab
Intervention Description
Recombinant human anti-VEGF IgG1 monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
(SP-4-2)-diamminedichloroplatinum(II)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
5-fluoro-2,4 (1H,3H)-pyrimidinedione
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)
Intervention Type
Drug
Intervention Name(s)
nab-Paclitaxel
Intervention Description
5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
Intervention Type
Drug
Intervention Name(s)
omega-3-acid ethyl esters
Intervention Description
Omega-3-acid ethyl esters
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Intervention Description
radiation
Intervention Type
Biological
Intervention Name(s)
ALT-803
Intervention Description
Recombinant human super agonist interleukin-15 (IL-15) complex
Intervention Type
Biological
Intervention Name(s)
ETBX-051
Intervention Description
Ad5 [E1-, E2b-]-Brachyury
Intervention Type
Biological
Intervention Name(s)
ETBX-061
Intervention Description
Ad5 [E1-, E2b-]-MUC1
Intervention Type
Biological
Intervention Name(s)
GI-6301
Intervention Description
Heat-killed S. cerevisiae yeast expressing the human Brachyury (hBrachyury) oncoprotein
Intervention Type
Biological
Intervention Name(s)
haNK
Intervention Description
NK-92 [CD16.158V, ER IL-2] (high-affinity activated Natural Killer cells)
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Description
Phase 1b primary endpoint
Time Frame
1 year
Title
Objective response rate by RECIST Version 1.1
Description
Phase 2 primary endpoint
Time Frame
1 year
Title
Objective response rate by irRC
Description
Phase 2 primary endpoint
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective response rate by RECIST Version 1.1
Description
Phase 1b secondary endpoint
Time Frame
1 year
Title
Objective response rate by irRC
Description
Phase 1b secondary endpoint
Time Frame
1 year
Title
Progression-free survival by RECIST Version 1.1
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Progression-free survival by irRC
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Overall survival
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Duration of response
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months)
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Quality of life by patient-reported outcome using Functional Assessment of Cancer Therapy-Melanoma (FACT-M) Questionnaire
Description
Phase 1b and Phase 2 secondary endpoint
Time Frame
2 years
Title
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
Description
Phase 2 secondary endpoint
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years.
Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
Histologically-confirmed metastatic or unresectable MCC with progression on or after anti-PD-L1 therapy (eg, avelumab).
ECOG performance status of 0 to 2.
Have at least 1 measurable lesion of ≥ 1.5 cm.
Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anti-cancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
Must be willing to provide blood samples for exploratory analyses, and if considered safe by the investigator, a tumor biopsy specimen at 8 weeks after the start of treatment.
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.
Exclusion Criteria:
History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
History of other active malignancies or brain metastasis except: controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable PSA (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. Subjects with a history of another malignancy must have > 5 years without evidence of disease.
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, Addison's disease, autoimmune disease associated with lymphoma).
History of organ transplant requiring immunosuppression.
History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
Requires whole blood transfusion to meet eligibility criteria.
Inadequate organ function, evidenced by the following laboratory results:
WBC count < 3,500 cells/mm3.
Absolute neutrophil count < 1,500 cells/mm3.
Platelet count < 100,000 cells/mm3.
Hemoglobin < 9 g/dL.
Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
AST (SGOT)) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
Serum creatinine > 2.0 mg/dL or 177 μmol/L.
INR or aPTT or PTT >1.5 × ULN (unless on therapeutic anti-coagulation).
Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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.
Positive results of screening test for HIV, HBV, or HCV.
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).
Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for 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.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy
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