Clinical Trials /

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

NCT04390399

Description:

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.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: QUILT-88
  • NCT ID: NCT04390399

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
N-803Cohort A Experimental Treatment Arm 2
Aldoxorubicin HClCohort A Experimental Treatment Arm 1
PD-L1 t-haNKCohort A Experimental Treatment Arm 3
Nab-paclitaxelCohort A Control Treatment Arm
GemcitabineCohort A Control Treatment Arm
CyclophosphamideCohort A Control Treatment Arm
5-FluorouracilCohort B Control Treatment Arm
LeucovorinCohort B Control Treatment Arm
Irinotecan liposomeCohort B Control Treatment Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort A Control Treatment ArmActive Comparator
  • Nab-paclitaxel
  • Gemcitabine
  • Cyclophosphamide
Cohort A Experimental Treatment Arm 1ExperimentalAldoxorubicin HCl added to Standard-of-Care Therapy
  • Aldoxorubicin HCl
  • Nab-paclitaxel
  • Gemcitabine
  • Cyclophosphamide
Cohort A Experimental Treatment Arm 2ExperimentalAldoxorubicin HCl + N-803 added to Standard-of-Care Therapy
  • N-803
  • Aldoxorubicin HCl
  • Nab-paclitaxel
  • Gemcitabine
  • Cyclophosphamide
Cohort A Experimental Treatment Arm 3ExperimentalAldoxorubicin HCl + N-803 + PD-L1 t-haNK added to Standard-of-Care Therapy
  • N-803
  • Aldoxorubicin HCl
  • PD-L1 t-haNK
  • Nab-paclitaxel
  • Gemcitabine
  • Cyclophosphamide
Cohort B Control Treatment ArmActive Comparator
  • 5-Fluorouracil
  • Leucovorin
  • Irinotecan liposome
Cohort B Experimental Treatment ArmExperimental
  • N-803
  • Aldoxorubicin HCl
  • PD-L1 t-haNK
  • Nab-paclitaxel
  • Gemcitabine
  • Cyclophosphamide

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunityBio, Inc.

Last Updated

June 18, 2020