QUILT-3.060: NANT Pancreatic Cancer Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
- Conditions
- Pancreatic Cancer
- Interventions
- Registration Number
- NCT03329248
- Lead Sponsor
- ImmunityBio, Inc.
- Brief Summary
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with pancreatic cancer who have progressed on or after previous SoC chemotherapy. Phase 2 will be based on Simon's two-stage optimal design.
- Detailed Description
Treatment will be administered in two phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws 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) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
- Age ≥ 18 years old.
- Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
- Histologically-confirmed pancreatic cancer with progression on or after SoC therapy.
- ECOG performance status of 0 to 2.
- Have at least 1 measurable lesion of ≥ 1.5 cm.
- Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen. 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.
- Must be willing to provide blood samples prior to the start of treatment on this study.
- Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, 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.
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History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity resulting from previous therapy.
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Within 5 years prior to first dose of study treatment, any evidence 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 prostate-specific antigen (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.
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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.
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Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
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History of organ transplant requiring immunosuppression.
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History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
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Requires whole blood transfusion to meet eligibility criteria.
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Inadequate organ function, evidenced by the following laboratory results:
- White blood cell (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).
- Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (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.
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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.
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Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
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Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
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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.
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Known hypersensitivity to any component of the study medication(s).
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Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
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Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 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.
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Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
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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.
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Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
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Concurrent participation in any interventional clinical trial.
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Pregnant and nursing women.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NANT Pancreatic Cancer Vaccine GI-4000 A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine ETBX-011 A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine ALT-803 A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine haNK for infusion A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine lovaza A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine avelumab A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine Fluorouracil A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine nab-Paclitaxel A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine Oxaliplatin A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine SBRT A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine Cyclophosphamide A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine Capecitabine A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine Leucovorin A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT NANT Pancreatic Cancer Vaccine bevacizumab A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) 30 days after last dose, up to 2 years (up to 1 year in each treatment phase) or until they experience confirmed progressive disease or unacceptable toxicity, withdrawn consent, or if the Investigator feels it is no longer in their best interest. Graded Using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
- Secondary Outcome Measures
Name Time Method Objective Response Rate by irRC Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 211 days. Objective Response Rate by RECIST Version 1.1 Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression, up to 211 days. Progression Free Survival by RECIST Version 1.1. Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death Progression Free Survival by irRC Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression or death Overall Survival Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until death Duration of Response (DOR) by RECIST Version 1.1 and irRC Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 211 days DOR was be defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occurs first. Responding subjects completed study follow-up or initiating a new anticancer therapy prior to documented PD were censored in the DOR analysis at the last known date the subject was progression free prior completing follow-up or initiating the new therapy.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by RECIST Version 1.1. Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 211 days Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.
Quality of Life by Patient Reported Outcomes (PRO) Up to 9 months PROs were assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep is compilation of general questions divided into five QOL subscales:
Physical Well-Being - Scores ranging from 0-28 Social/Family Well-Being - Scores ranging from 0-28 Emotional Well-Being - Scores ranging from 0-24 Functional Well-Being - Scores ranging from 0-28 Additional Concerns - Scores ranging from 0-72 It uses 5-point Likert-type response categories ranging from 0 = 'not at all' to 4 = 'very much'.
The higher scales and subscales indicate better quality of life. Negatively worded items were reverse scored. If the missing for each subscale was less than 50%, the prorating scores were computed for the subscale.Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by irRC Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 211 days Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.
Trial Locations
- Locations (1)
Chan Soon-Shiong Institute for Medicine
🇺🇸El Segundo, California, United States