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

• ClinicalTrials.gov Identifier: NCT03136406
• Recruitment Status: Unknown
• First Posted: May 2, 2017
• Last Update Posted: August 12, 2020
• Sponsor: ImmunityBio, Inc.
• Information provided by (Responsible Party): ImmunityBio, Inc.

Study Description

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 Standard of Care first line therapy and chemotherapy.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: Cyclophosphamide; Drug: Oxaliplatin; Drug: Capecitabine; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-paclitaxel; Biological: bevacizumab; Biological: avelumab; Biological: ALT-803; Biological: aNK for Infusion; Biological: ETBX-011; Biological: GI-4000	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
• Actual Study Start Date: August 14, 2017
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: April 2021

Arms and Interventions

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: 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: 5-Fluorouracil; 5-fluoro-2,4 (1H,3H)-pyrimidinedione; 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: 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: ALT-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Biological: aNK for Infusion; NK-92 cells; Biological: ETBX-011; Ad5 [E1-, E2b-]-CEA; Biological: GI-4000; Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03. [ Time Frame: 8 weeks ]
   Phase 1b primary endpoint
2. Objective response rate by RECIST [ Time Frame: 1 year ]
   Phase 2 primary endpoint
3. Objective response rate by irRC [ Time Frame: 1 year ]
   Phase 2 primary endpoint

Secondary Outcome Measures :

1. Objective response rate by RECIST [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
2. Objective response rate by irRC [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
3. Progression-free survival by RECIST during Phase 1b [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
4. Progression-free survival by irRC during Phase 1b [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
5. Overall survival [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
6. Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 8 weeks ]
   Phase 1b secondary endpoint
7. Progression-free survival by RECIST during Phase 2 [ Time Frame: 1 year ]
   Phase 2 secondary endpoint
8. Progression-free survival by irRC during Phase 2 [ Time Frame: 1 year ]
   Phase 2 secondary endpoint
9. Overall survival [ Time Frame: 1 year ]
   Phase 2 secondary endpoint
10. Duration of response [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
11. Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months). [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
12. Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
13. Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03. [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Chan Soon-Shiong Institute for Medicine

El Segundo, California, United States, 90245

Sponsors and Collaborators

ImmunityBio, Inc.

More Information

• Responsible Party: ImmunityBio, Inc.
• ClinicalTrials.gov Identifier: NCT03136406
• Other Study ID Numbers: QUILT-3.039
• First Posted: May 2, 2017
• Last Update Posted: August 12, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Leucovorin; Paclitaxel; Cyclophosphamide; Bevacizumab; Fluorouracil; Capecitabine; Oxaliplatin; Avelumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological