- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03167164
QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy
March 17, 2021 updated by: ImmunityBio, Inc.
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
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.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
- Biological: ALT-803
- Drug: Cyclophosphamide
- Drug: Capecitabine
- Drug: Cisplatin
- Biological: ETBX-061
- Biological: ETBX-051
- Drug: Leucovorin
- Biological: Avelumab
- Biological: Bevacizumab
- Drug: 5-fluorouracil
- Drug: nab-Paclitaxel
- Drug: omega-3-acid ethyl esters
- Radiation: Stereotactic Body Radiation Therapy
- Biological: GI-6301
- Biological: haNK
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.
Study Type
Interventional
Phase
- Phase 2
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NANT MCC Vaccine
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. |
Recombinant human super agonist interleukin-15 (IL-15) complex
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
(SP-4-2)-diamminedichloroplatinum(II)
Ad5 [E1-, E2b-]-MUC1
Ad5 [E1-, E2b-]-Brachyury
Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
Recombinant human anti-VEGF IgG1 monoclonal antibody
5-fluoro-2,4 (1H,3H)-pyrimidinedione
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
Omega-3-acid ethyl esters
radiation
Heat-killed S. cerevisiae yeast expressing the human Brachyury (hBrachyury) oncoprotein
NK-92 [CD16.158V,
ER IL-2] (high-affinity activated Natural Killer cells)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate by irRC
Time Frame: 1 year
|
Phase 2 primary endpoint
|
1 year
|
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Time Frame: 1 year
|
Phase 1b primary endpoint
|
1 year
|
Objective response rate by RECIST Version 1.1
Time Frame: 1 year
|
Phase 2 primary endpoint
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate by RECIST Version 1.1
Time Frame: 1 year
|
Phase 1b secondary endpoint
|
1 year
|
Objective response rate by irRC
Time Frame: 1 year
|
Phase 1b secondary endpoint
|
1 year
|
Progression-free survival by RECIST Version 1.1
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Progression-free survival by irRC
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Overall survival
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Duration of response
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months)
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Quality of life by patient-reported outcome using Functional Assessment of Cancer Therapy-Melanoma (FACT-M) Questionnaire
Time Frame: 2 years
|
Phase 1b and Phase 2 secondary endpoint
|
2 years
|
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
December 1, 2017
Primary Completion (Anticipated)
January 1, 2019
Study Completion (Anticipated)
March 1, 2019
Study Registration Dates
First Submitted
May 23, 2017
First Submitted That Met QC Criteria
May 23, 2017
First Posted (Actual)
May 25, 2017
Study Record Updates
Last Update Posted (Actual)
March 19, 2021
Last Update Submitted That Met QC Criteria
March 17, 2021
Last Verified
October 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Virus Diseases
- Infections
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- DNA Virus Infections
- Tumor Virus Infections
- Neuroendocrine Tumors
- Polyomavirus Infections
- Carcinoma, Neuroendocrine
- Carcinoma
- Carcinoma, Merkel Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Cyclophosphamide
- Paclitaxel
- Cisplatin
- Fluorouracil
- Capecitabine
- Bevacizumab
- Leucovorin
- Avelumab
Other Study ID Numbers
- QUILT-3.045
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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