Pancreatic Cancer
Conditions
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.
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.
Interventions
DRUGCyclophosphamide
2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
DRUGOxaliplatin
cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum
DRUGCapecitabine
5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine
DRUG5-Fluorouracil
5-fluoro-2,4 (1H,3H)-pyrimidinedione
DRUGLeucovorin
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
DRUGnab-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
BIOLOGICALbevacizumab
Recombinant human anti-VEGF IgG1 monoclonal
BIOLOGICALavelumab
Recombinant human anti-PD-L1 IgG1 monoclonal antibody
BIOLOGICALALT-803
Recombinant human super agonist interleukin-15 (IL-15) complex
BIOLOGICALaNK for Infusion
NK-92 cells
BIOLOGICALETBX-011
Ad5 \[E1-, E2b-\]-CEA
BIOLOGICALGI-4000
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins
Sponsors
ImmunityBio, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events | 30 days after last dose, up to 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Cyclophosphamide: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
Oxaliplatin: cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum
Capecitabine: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine
5-Fluorouracil: 5-fluoro-2,4 (1H,3H)-pyrimidinedione
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
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
bevacizumab: Recombinant human anti-VEGF IgG1 monoclonal
avelumab: Recombinant human anti-PD-L1 IgG1 monoclonal antibody
ALT-803: Recombinant human super agonist interleukin-15 (IL-15) complex
aNK for Infusion: NK-92 cells
ETBX-011: Ad5 \[E1-, E2b-\]-CEA
GI-4000: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Treatment Discontinued-Investigator Decision | 3 |
Baseline characteristics
| Characteristic | NANT Pancreatic Cancer Vaccine |
|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Histologically-confirmed pancreatic cancer with progression on or after SoC therapy. | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Number of Participants With Adverse Events
Time frame: 30 days after last dose, up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NANT Pancreatic Cancer Vaccine | Number of Participants With Adverse Events | 3 Participants |