Clinical Trials /

QUILT 2.023: A Study of N-803 in Combination With Current Standard of Care vs Standard of Care as First-Line Treatment for Patients With Stage 3 or 4 NSCLC.

NCT03520686

Description:

This is a phase 3, open-label, 3-cohort, randomized study to compare the safety and efficacy of N-803 in combination with the current standard of care (experimental arms) versus standard of care alone (control arms), as first-line treatment for subjects with stage 3 or 4 advanced or metastatic NSCLC. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the investigator feels that it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months after the first dose of study drug.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: QUILT 2.023: A Study of N-803 in Combination With Current Standard of Care vs Standard of Care as First-Line Treatment for Patients With Stage 3 or 4 NSCLC.
  • Official Title: QUILT 2.023: A Phase 3, Open-Label, 3-Cohort Randomized Study of N-803, in Combination With Current Standard of Care VS Standard of Care as First-Line Treatment for Patients With Advanced or Metastatic NSCLC.

Clinical Trial IDs

  • ORG STUDY ID: QUILT2.023
  • NCT ID: NCT03520686

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
N-803 + PembrolizumabCohort A (Experimental)
N-803 + Carboplatin + Nab-paclitaxel + PembrolizumabCohort B (Experimental)
N-803 + Cisplatin or Carboplatin + Pembrolizumab + PemetrexedCohort C (Experimental)
PembrolizumabCohort A (Control)
Carboplatin + Nab-paclitaxel or Paclitaxel + PembrolizumabCohort B (Control)
Cisplatin or Carboplatin + Pembrolizumab + PemetrexedCohort C (Control)

Purpose

This is a phase 3, open-label, 3-cohort, randomized study to compare the safety and efficacy of N-803 in combination with the current standard of care (experimental arms) versus standard of care alone (control arms), as first-line treatment for subjects with stage 3 or 4 advanced or metastatic NSCLC. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the investigator feels that it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months after the first dose of study drug.

Trial Arms

NameTypeDescriptionInterventions
Cohort A (Experimental)Experimental
  • N-803 + Pembrolizumab
Cohort B (Experimental)Experimental
  • N-803 + Carboplatin + Nab-paclitaxel + Pembrolizumab
Cohort C (Experimental)Experimental
  • N-803 + Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed
Cohort A (Control)Active Comparator
  • Pembrolizumab
Cohort B (Control)Active Comparator
  • Carboplatin + Nab-paclitaxel or Paclitaxel + Pembrolizumab
Cohort C (Control)Active Comparator
  • Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years old.

          2. Able to understand and provide a signed informed consent that fulfills the relevant
             IRB or Independent Ethics Committee (IEC) guidelines.

          3. Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease
             must not be candidates for treatment with surgical resection or chemoradiation.

          4. Subjects must not have received prior systemic chemotherapy for advanced or metastatic
             NSCLC. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months
             before diagnosis of metastatic disease. Subject's with newly-diagnosed stage 4 NSCLC
             may have previously received systemic chemotherapy for stage 3 NSCLC.

          5. For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as
             determined by an FDA-approved test.

          6. The subject's tumor must not harbor an EGFR sensitizing (activating) mutation or ALK
             translocation or targetable genomic aberration in BRAF, ROS1 or NTRK. EGFR sensitizing
             mutations are those mutations that are amenable to treatment with tyrosine kinase
             inhibitors including erlotinib, gefitinib, or afatinib. Investigators must be able to
             produce the source documentation of the EGFR mutation, ALK translocation, and BRAF,
             ROS1, and NTRK status. If any of the genomic changes described above are detected,
             additional information regarding the mutation status of other molecules is not
             required. If unable to test for these molecular changes, formalin fixed paraffin
             embedded tumor tissue of any age should be submitted to a central laboratory
             designated by the Sponsor for such testing. Subjects will not be randomized until the
             EGFR , BRAFT, ROS1, and NTRK mutation status and ALK translocation status is available
             in source documentation at the site.

          7. ECOG performance status of 0 or 1.

          8. Measurable tumor lesions according to RECIST 1.1.

          9. Must be willing to release tumor biopsy specimen used for diagnosis of advanced or
             metastatic NSCLC (if available) for exploratory tumor molecular profiling. If tumor
             biopsy specimen is not available, subjects can still be enrolled.

         10. Must be willing to provide blood samples prior to the start of treatment on this study
             for exploratory tumor molecular profiling analysis.

         11. Must be willing to provide a tumor biopsy specimen 9 weeks after the start of
             treatment for exploratory analyses, if considered safe by the Investigator.

         12. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol

         13. 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 for up to 1 year after completion of therapy, and
             non-sterile male subjects must agree to use a condom for up to 4 months after
             treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
             tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
             spermicide, intrauterine devices (IUDs), hormonal therapy, and abstinence.

        Exclusion Criteria:

          1. 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.

          2. A history of prior malignancy with the following exceptions: cancer treated with
             curative therapy with no disease recurrence for >3 years, non-metastatic prostate
             cancer controlled with hormonal therapy, or under observation; non-metastatic thyroid
             cancer; basal or squamous cell carcinoma of the skin, superficial bladder cancer, or
             in situ cervical cancer that has undergone successful definitive resection.

          3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
             disease, or autoimmune disease associated with lymphoma).

          4. History of organ transplant requiring immunosuppression; or history of pneumonitis or
             interstitial lung disease requiring treatment with systemic steroids; or a history of
             receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days
             prior to study initiation. Daily steroid replacement therapy (eg, prednisone or
             hydrocortisone) and corticosteroid use to manage AEs are permitted.

          5. Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of
             study initiation.

          6. Requirement for other forms of anticancer treatment while on trial, including
             maintenance therapy, other radiation therapy, and/or surgery. Palliative radiation is
             permitted.

          7. Known CNS metastases or carcinomatous meningitis. Subjects with previously treated,
             stable CNS metastases (no evidence of progression for ≥ 4 weeks, and resolution of
             neurologic symptoms to baseline state) are permitted in this study.

          8. History of receiving a live vaccine 30 days prior to study treatment.

          9. History of human immunodeficiency virus (HIV), or known active hepatitis B or C
             infection.

         10. An active infection requiring systemic IV therapy.

         11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
             colitis).

         12. Inadequate organ function, evidenced by the following laboratory results:

               1. Absolute neutrophil count < 1,500 cells/mm3.

               2. Platelet count < 100,000 cells/mm3.

               3. Total bilirubin greater the upper limit of normal (ULN; unless the subject has
                  documented Gilbert's syndrome).

               4. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
                  > 1.5 × ULN.

               5. Alkaline phosphatase (ALP) levels > 2.5 × ULN.

               6. Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min
                  (using the Cockcroft-Gault formula)

         13. 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. Subjects with
             uncontrolled hypertension should be medically managed on a stable regimen to control
             hypertension prior to study entry.

         14. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
             continuous oxygen therapy.

         15. Known hypersensitivity to any component of the study medication(s).

         16. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
             reaction with any of the study medications.

         17. Participation in an investigational drug study or history of receiving any
             investigational treatment within 30 days prior to screening for this study, except for
             testosterone-lowering therapy in men with prostate cancer.

         18. Assessed by the Investigator to be unable or unwilling to comply with the requirements
             of the protocol.

         19. Concurrent participation in any interventional clinical trial.

         20. Pregnant and nursing women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:24 Months
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR
Measure:Duration of Response (DOR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR.
Measure:PFS
Time Frame:24 Months
Safety Issue:
Description:Defined by iRECIST based on BICR.
Measure:Overall Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by iRECIST based on BICR.
Measure:Duration of Response (DOR)
Time Frame:24 Months
Safety Issue:
Description:Defined by iRECIST based on BICR.
Measure:Disease Control Rate (DCR)
Time Frame:2 Months
Safety Issue:
Description:Confirmed CR, PR, or SD lasting for at least 2 months by RECIST Version 1.1 based on BICR
Measure:Quality of Life based on Patient Reported Outcomes Questionnaires
Time Frame:24 Months
Safety Issue:
Description:FACT-L

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Altor BioScience

Trial Keywords

  • Pembrolizumab
  • N-803
  • Non-Small Cell Lung Cancer
  • Immunotherapy
  • Carboplatin
  • Cisplatin
  • Nab-paclitaxel
  • Paclitaxel
  • Pemetrexed
  • Chemotherapy

Last Updated

July 29, 2020