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Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for First and Second Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04390399
Recruitment Status : Recruiting
First Posted : May 15, 2020
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
ImmunityBio, Inc.

Tracking Information
First Submitted Date  ICMJE May 7, 2020
First Posted Date  ICMJE May 15, 2020
Last Update Posted Date September 3, 2020
Actual Study Start Date  ICMJE July 21, 2020
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2020)
Progression Free Survival (PFS) per Response Criteria in Solid Tumors (RECIST) V1.1 [ Time Frame: 8 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
  • Objective response rate (ORR), Complete response (CR) rate, and Disease Control Rate (DCR) by Response Criteria in Solid Tumors (RECIST) V1.1 [ Time Frame: 2 years ]
  • Overall Survival [ Time Frame: 2 years ]
  • Quality of Life (QoL) by Patient Reported Outcomes (PROs) using the Functional Assessment of Cancer Therapy - Hepatobiliary Cancer (FACT-Hep) Questionnaire [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2020)
  • Objective response rate (ORR), Complete response (CR) rate, and Disease Control Rate (DCR) by Response Criteria in Solid Tumors (RECIST) V1.1 [ Time Frame: 2 years ]
  • Overall Survival [ Time Frame: 2 years ]
  • Quality of Life (QoL) by Patient Reported Outcomes (PROs) using the Function Assessment of Cancer Therapy - Hepatobiliary Cancer (FACT-Hep) Questionnaire [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for First and Second Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer
Official Title  ICMJE Open-label, Randomized, Comparative Phase 2 Study of Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for First and Second Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer
Brief Summary This is a phase 2, randomized, two-cohort, open-label study to evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with aldoxorubicin HCl, N-803, and PD-L1 t haNK in subjects with locally advanced or metastatic pancreatic cancer. Each treatment setting (ie, first line maintenance, or second or later line) will be evaluated independently as a separate cohort.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Biological: N-803
    Recombinant human super agonist interleukin-15 (IL-15) complex
  • Drug: Aldoxorubicin HCl
    Aldoxorubicin hydrochloride
  • Biological: PD-L1 t-haNK
    PD-L1 t-haNK suspension for infusion
  • 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
  • Drug: Gemcitabine
    2', 2'-difluoro 2'deoxycytidine, dFdC
  • Drug: Cyclophosphamide
    2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
  • 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
  • Procedure: SBRT
    Stereotactic Body Radiation Therapy
  • Drug: Irinotecan liposome
    Irinotecan hydrochloride trihydrate is (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-yl-[1,4'bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate
Study Arms  ICMJE
  • Active Comparator: Cohort A Control Treatment Arm
    Interventions:
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Cyclophosphamide
    • Procedure: SBRT
  • Experimental: Cohort A Experimental Treatment Arm 1
    Aldoxorubicin HCl added to Standard-of-Care Therapy
    Interventions:
    • Drug: Aldoxorubicin HCl
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Cyclophosphamide
    • Procedure: SBRT
  • Experimental: Cohort A Experimental Treatment Arm 2
    Aldoxorubicin HCl + N-803 added to Standard-of-Care Therapy
    Interventions:
    • Biological: N-803
    • Drug: Aldoxorubicin HCl
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Cyclophosphamide
    • Procedure: SBRT
  • Experimental: Cohort A Experimental Treatment Arm 3
    Aldoxorubicin HCl + N-803 + PD-L1 t-haNK added to Standard-of-Care Therapy
    Interventions:
    • Biological: N-803
    • Drug: Aldoxorubicin HCl
    • Biological: PD-L1 t-haNK
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Cyclophosphamide
    • Procedure: SBRT
  • Active Comparator: Cohort B Control Treatment Arm
    Interventions:
    • Drug: 5-Fluorouracil
    • Drug: Leucovorin
    • Drug: Irinotecan liposome
  • Experimental: Cohort B Experimental Treatment Arm
    Interventions:
    • Biological: N-803
    • Drug: Aldoxorubicin HCl
    • Biological: PD-L1 t-haNK
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Cyclophosphamide
    • Procedure: SBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 1, 2020)
248
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2020)
268
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
  3. Have histologically confirmed unresectable, locally advanced or metastatic pancreatic cancer.

    1. For Cohort A, subjects must have initially received, or are currently receiving, continuous treatment with gemcitabine plus nab-paclitaxel for at least 16 weeks and have confirmed PR, CR, or SD prior to receiving first-line maintenance therapy on this study. Duration of actual initial treatment may be unlimited as long as no evidence of disease progression is noted by the Investigator at the time of randomization.
    2. For Cohort B, subjects must have PD after receiving initial treatment with FOLFOX, FOLFIRINOX, and/or a gemcitabine-based therapy for pancreatic cancer. Subjects who discontinued prior therapy due to toxicity, intolerance, or available therapy was clinically contraindicated are allowed.
  4. ECOG PS of 0 or 1.
  5. Have at least 1 measurable lesion and/or non-measurable disease evaluable in accordance with RECIST V1.1.
  6. Must have a tumor biopsy specimen and be willing to release the specimen for exploratory tumor molecular profiling. Specimen may be either an FFPE tumor biopsy specimen obtained following the conclusion of the most recent anticancer treatment or the subject should 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. A tumor biopsy specimen is not required for subjects who have tumor molecular profiling results from previous NantOmics testing.
  7. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  8. 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 while on study and for at least 5 months after the last dose of study treatment. Non-sterile male subjects must agree to use a condom while on study and for up to 5 months after the last dose of study treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, IUDs, oral contraceptives, and abstinence.

Exclusion Criteria

  1. Body weight ≤ 50 kg at screening.
  2. 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.
  3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
  4. For Cohort A only: tumors harboring germline BRCA1/2 mutations.
  5. For Cohort B only: previous treatment with liposomal irinotecan for advanced or metastatic pancreatic cancer.
  6. History of organ transplant requiring immunosuppression.
  7. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  8. Inadequate organ function, evidenced by the following laboratory results:

    1. Absolute neutrophil count (ANC) < 1000 cells/mm3.
    2. Platelet count < 100,000 cells/mm3.
    3. Hemoglobin < 9 g/dL.
    4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    6. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.
  9. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 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.
  10. Serious myocardial dysfunction defined by ECHO as an absolute LVEF ≤ 45%.
  11. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  12. 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.
  13. Known hypersensitivity to any component of the study medication(s).
  14. 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.
  15. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  16. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to dosing for this study, except for testosterone-lowering therapy in men with prostate cancer.
  17. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  18. Concurrent participation in any interventional clinical trial.
  19. Pregnant and nursing women. A negative serum pregnancy test during screening and a negative pregnancy test within 72 hours prior to the first dose must be documented before study drug is administered to a female subject of child-bearing potential.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lennie Sender, MD 714-615-2350 Lennie.Sender@NantKwest.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04390399
Other Study ID Numbers  ICMJE QUILT-88
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ImmunityBio, Inc.
Study Sponsor  ICMJE ImmunityBio, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account ImmunityBio, Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP