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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.

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Biological: N-803 Drug: Aldoxorubicin HCl Biological: PD-L1 t-haNK Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Cyclophosphamide Drug: 5-Fluorouracil Drug: Leucovorin Procedure: SBRT Drug: Irinotecan liposome Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 248 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 21, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Cohort A Control Treatment Arm 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

Procedure: SBRT
Stereotactic Body Radiation Therapy

Experimental: Cohort A Experimental Treatment Arm 1
Aldoxorubicin HCl added to Standard-of-Care Therapy
Drug: Aldoxorubicin HCl
Aldoxorubicin hydrochloride

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

Procedure: SBRT
Stereotactic Body Radiation Therapy

Experimental: Cohort A Experimental Treatment Arm 2
Aldoxorubicin HCl + N-803 added to Standard-of-Care Therapy
Biological: N-803
Recombinant human super agonist interleukin-15 (IL-15) complex

Drug: Aldoxorubicin HCl
Aldoxorubicin hydrochloride

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

Procedure: SBRT
Stereotactic Body Radiation Therapy

Experimental: Cohort A Experimental Treatment Arm 3
Aldoxorubicin HCl + N-803 + PD-L1 t-haNK added to Standard-of-Care Therapy
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

Procedure: SBRT
Stereotactic Body Radiation Therapy

Active Comparator: Cohort B Control Treatment Arm 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: 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

Experimental: Cohort B Experimental Treatment Arm 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

Procedure: SBRT
Stereotactic Body Radiation Therapy




Primary Outcome Measures :
  1. Progression Free Survival (PFS) per Response Criteria in Solid Tumors (RECIST) V1.1 [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. Overall Survival [ Time Frame: 2 years ]
  3. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04390399


Contacts
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Contact: Lennie Sender, MD 714-615-2350 Lennie.Sender@NantKwest.com

Locations
Layout table for location information
United States, California
Chan Soon-Shiong Institute for Medicine Recruiting
El Segundo, California, United States, 90245
Contact: Paula Bradshaw    213-266-5600    paula.bradshaw@cssifm.org   
Principal Investigator: Chaitali Nangia, MD         
Hoag memorial Presbyterian Hospital Recruiting
Newport Beach, California, United States, 92663
Contact: Rosie Blancas    949-764-4430    Rosie.Blancas1@hoag.org   
Principal Investigator: Tara Seery, MD         
Sponsors and Collaborators
ImmunityBio, Inc.
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Responsible Party: ImmunityBio, Inc.
ClinicalTrials.gov Identifier: NCT04390399    
Other Study ID Numbers: QUILT-88
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Leucovorin
Gemcitabine
Paclitaxel
Cyclophosphamide
Fluorouracil
Irinotecan
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
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents