Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer

Open-label, Randomized, Comparative Phase 2 Study of Combination Immunotherapy Plus Standard-of-care Chemotherapy Versus Standard-of-care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer

This is a phase 2, three-cohort (2 randomized and 1 single-arm), 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, second line, or third line or greater) will be evaluated independently as a separate cohort.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Biological: N-803; Drug: Aldoxorubicin HCl; Procedure: SBRT; Drug: Nab-paclitaxel; Drug: Gemcitabine; Biological: PD-L1 t-haNK; Drug: Irinotecan liposome

• Study Type: Interventional
• Enrollment (Estimated): 328
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • El Segundo, California, United States, 90245
      • Chan Soon-Shiong Institute for Medicine
    • Newport Beach, California, United States, 92663
      • Hoag memorial Presbyterian Hospital
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

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, or a gemcitabine- or paclitaxel-based therapy for pancreatic cancer.

      Subjects who discontinued prior therapy due to toxicity, intolerance, or available therapy was clinically contraindicated are allowed.

   3. For Cohort C, subjects must have PD after receiving at least 2 lines of therapy for pancreatic cancer, including but not limited to neoadjuvant, adjuvant, and/or metastatic settings.
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. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
7. 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 ≤ 40 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 two times 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. Albumin <3.0.
   10. Ascites requiring paracentesis.

   Each site should use its own institution's ULN to determine eligibility.

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. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
11. 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.
12. Known hypersensitivity to any component of the study medication(s).
13. 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.
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
15. 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 or FDA-authorized drugs for the prevention and treatment of COVID-19.
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
17. Concurrent participation in any interventional clinical trial.
18. 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.
19. Any other cancer within the past 5 years that is progressing or requires active treatment, or any previous cancer treatment within the last 5 years that included gemcitabine or nab-paclitaxel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort A Control Treatment Arm; SBRT + gemcitabine + nab-paclitaxel	Procedure: SBRT; Stereotactic Body Radiation Therapy; 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
Experimental: Cohort A Experimental Treatment Arm 1; SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin HCl + N-803	Drug: Cyclophosphamide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; Biological: N-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Drug: Aldoxorubicin HCl; Aldoxorubicin hydrochloride; Procedure: SBRT; Stereotactic Body Radiation Therapy; 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
Experimental: Cohort A Experimental Treatment Arm 2; SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK	Drug: Cyclophosphamide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; Biological: N-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Drug: Aldoxorubicin HCl; Aldoxorubicin hydrochloride; Procedure: SBRT; Stereotactic Body Radiation Therapy; 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; Biological: PD-L1 t-haNK; PD-L1 t-haNK suspension for infusion
Active Comparator: Cohort B Control Treatment Arm; Irinotecan liposome + 5-FU/leucovorin	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; 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; SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK	Drug: Cyclophosphamide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; Biological: N-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Drug: Aldoxorubicin HCl; Aldoxorubicin hydrochloride; Procedure: SBRT; Stereotactic Body Radiation Therapy; 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; Biological: PD-L1 t-haNK; PD-L1 t-haNK suspension for infusion
Experimental: Cohort C Experimental Treatment Arm; SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin + N-803 + PD-L1 t-haNK	Drug: Cyclophosphamide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; Biological: N-803; Recombinant human super agonist interleukin-15 (IL-15) complex; Drug: Aldoxorubicin HCl; Aldoxorubicin hydrochloride; Procedure: SBRT; Stereotactic Body Radiation Therapy; 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; Biological: PD-L1 t-haNK; PD-L1 t-haNK suspension for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Response Criteria in Solid Tumors (RECIST) V1.1	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		2 years
Objective response rate (ORR), Complete response (CR) rate, and Disease Control Rate (DCR)	Response Criteria in Solid Tumors (RECIST) V1.1	2 years
Quality of Life (QoL)	Patient Reported Outcomes (PROs) using the Functional Assessment of Cancer Therapy - Hepatobiliary Cancer (FACT-Hep) Questionnaire	2 years

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 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; Enzyme Inhibitors; 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; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Cyclophosphamide; Paclitaxel; Fluorouracil; Leucovorin; Irinotecan; Gemcitabine
• Other Study ID Numbers: QUILT-88

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