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

NCT04390399 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: QUILT-88
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Response Criteria in Solid Tumors (RECIST) V1.1

  8 weeks

Secondary Outcomes (3)

• Objective response rate (ORR), Complete response (CR) rate, and Disease Control Rate (DCR)

  2 years

• Overall Survival (OS)

  2 years

• Quality of Life (QoL)

  2 years

Study Arms (6)

Cohort A Control Treatment Arm

ACTIVE COMPARATOR

SBRT + gemcitabine + nab-paclitaxel

Drug: Nab-paclitaxel; Drug: Gemcitabine; Procedure: SBRT

Cohort A Experimental Treatment Arm 1

EXPERIMENTAL

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin HCl + N-803

Biological: N-803; Drug: Aldoxorubicin HCl; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cyclophosphamide; Procedure: SBRT

Cohort A Experimental Treatment Arm 2

EXPERIMENTAL

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK

Biological: N-803; Drug: Aldoxorubicin HCl; Biological: PD-L1 t-haNK; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cyclophosphamide; Procedure: SBRT

Cohort B Control Treatment Arm

ACTIVE COMPARATOR

Irinotecan liposome + 5-FU/leucovorin

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Irinotecan liposome

Cohort B Experimental Treatment Arm

EXPERIMENTAL

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK

Biological: N-803; Drug: Aldoxorubicin HCl; Biological: PD-L1 t-haNK; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cyclophosphamide; Procedure: SBRT

Cohort C Experimental Treatment Arm

EXPERIMENTAL

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin + N-803 + PD-L1 t-haNK

Biological: N-803; Drug: Aldoxorubicin HCl; Biological: PD-L1 t-haNK; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cyclophosphamide; Procedure: SBRT

Interventions

N-803 BIOLOGICAL

Recombinant human super agonist interleukin-15 (IL-15) complex

Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

Aldoxorubicin HCl DRUG

Aldoxorubicin hydrochloride

Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

PD-L1 t-haNK BIOLOGICAL

PD-L1 t-haNK suspension for infusion

Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

Nab-paclitaxel DRUG

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

Cohort A Control Treatment Arm; Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

Gemcitabine DRUG

2', 2'-difluoro 2'deoxycytidine, dFdC

Cohort A Control Treatment Arm; Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

Cyclophosphamide DRUG

2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

5-Fluorouracil DRUG

5-fluoro-2,4 (1H,3H)-pyrimidinedione

Cohort B Control Treatment Arm

Leucovorin DRUG

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

Cohort B Control Treatment Arm

SBRT PROCEDURE

Stereotactic Body Radiation Therapy

Cohort A Control Treatment Arm; Cohort A Experimental Treatment Arm 1; Cohort A Experimental Treatment Arm 2; Cohort B Experimental Treatment Arm; Cohort C Experimental Treatment Arm

Irinotecan liposome DRUG

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

Cohort B Control Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Have histologically confirmed unresectable, locally advanced or metastatic pancreatic cancer.
• 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.
• 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.
• 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.
• ECOG PS of 0 or 1.
• Have at least 1 measurable lesion and/or non-measurable disease evaluable in accordance with RECIST V1.1.
• 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 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.

You may not qualify if:

• Body weight ≤ 40 kg at screening.
• 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).
• For Cohort A only: tumors harboring germline BRCA1/2 mutations.
• For Cohort B only: previous treatment with liposomal irinotecan for advanced or metastatic pancreatic cancer.
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count (ANC) \< 1000 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Hemoglobin \< 9 g/dL.
• Total bilirubin greater than two times 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 (ALP) 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.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (4)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

Hoag memorial Presbyterian Hospital

Newport Beach, California, 92663, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ALT-803; 130-nm albumin-bound paclitaxel; Gemcitabine; Cyclophosphamide; Fluorouracil; Leucovorin; irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 15, 2020
• Study Start: July 21, 2020
• Primary Completion: October 13, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)