QUILT-3.039: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

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 Standard of Care first line therapy and chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: 5-Fluorouracil; Biological: ETBX-011; Biological: GI-4000; Biological: ALT-803; Drug: Cyclophosphamide; Drug: Oxaliplatin; Drug: Capecitabine; Drug: nab-paclitaxel; Biological: bevacizumab; Biological: avelumab; Biological: aNK for Infusion

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 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 throughout phase 2 until the subject experiences PD or unacceptable toxicity, withdraws consent, or the investigator feels it is no longer in the subject's best interest to continue treatment.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • El Segundo, California, United States, 90245
      • Chan Soon-Shiong Institute for Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or 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 and/or non-measurable disease evaluable according to RECIST Version 1.1.
• Must have a recent tumor biopsy specimen 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.
• 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 with child-bearing potential and non-sterile males.

Exclusion Criteria:

• History of persistent grade 2 or higher (CTCAE Version 4.03) hematological 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 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. 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:

  • 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.
  • International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (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 human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (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. See Excluded Medications list.
• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NANT Pancreatic Cancer Vaccine; A combination of agents will be administered to subjects in this study: cyclophosphamide, oxaliplatin, capecitabine, fluorouracil, leucovorin, nab-paclitaxel, bevacizumab, avelumab, ALT-803, aNK, GI-4000, and ETBX-011.

Drug: Leucovorin; L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt; Drug: 5-Fluorouracil; 5-fluoro-2,4 (1H,3H)-pyrimidinedione; Biological: ETBX-011; Ad5 [E1-, E2b-]-CEA; Biological: GI-4000; Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins; Biological: ALT-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Drug: Cyclophosphamide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; Drug: Oxaliplatin; cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum; Drug: Capecitabine; 5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine; Drug: nab-paclitaxel; Benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-y1ester,(αR,βS)-(9CI) bound to albumin; Biological: bevacizumab; Recombinant human anti-VEGF IgG1 monoclonal; Biological: avelumab; Recombinant human anti-PD-L1 IgG1 monoclonal antibody; Biological: aNK for Infusion; NK-92 cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	30 days after last dose, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate by RECIST	Phase 1b secondary endpoint	8 weeks
Objective response rate by irRC	Phase 1b secondary endpoint	8 weeks
Progression-free survival by RECIST during Phase 1b	Phase 1b secondary endpoint	8 weeks
Progression-free survival by irRC during Phase 1b	Phase 1b secondary endpoint	8 weeks
Overall survival	Phase 1b secondary endpoint	8 weeks
Patient-reported outcomes of pancreatic cancer symptoms	Phase 1b secondary endpoint	8 weeks
Progression-free survival by RECIST during Phase 2	Phase 2 secondary endpoint	1 year
Progression-free survival by irRC during Phase 2	Phase 2 secondary endpoint	1 year
Overall survival	Phase 2 secondary endpoint	1 year
Duration of response	Phase 2 secondary endpoint	1 year
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months).	Phase 2 secondary endpoint	1 year
Patient-reported outcomes of pancreatic cancer symptoms	Phase 2 secondary endpoint	1 year
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03.	Phase 2 secondary endpoint	1 year

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2017
• Primary Completion (Actual): November 22, 2017
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): May 2, 2017

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; 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; Fluorouracil; Capecitabine; Oxaliplatin; Bevacizumab; Leucovorin; Avelumab
• Other Study ID Numbers: QUILT-3.039

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