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QUILT-2.023: A Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC.

NCT03520686

Description:

This is a phase 2, open-label, randomized study to compare the safety and efficacy of combination therapy with ALT-803 and pembrolizumab (experimental arm) versus pembrolizumab alone (control arm), as first-line treatment for subjects with metastatic NSCLC in which pembrolizumab is indicated for first-line treatment.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-2.023: A Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC.
  • Official Title: A Phase 2, Open-Label, Randomized Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC.

Clinical Trial IDs

  • ORG STUDY ID: QUILT-2.023
  • NCT ID: NCT03520686

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
ALT-803 + PembrolizumabGroup A
PembrolizumabGroup B

Purpose

This is a phase 2, open-label, randomized study to compare the safety and efficacy of combination therapy with ALT-803 and pembrolizumab (experimental arm) versus pembrolizumab alone (control arm), as first-line treatment for subjects with metastatic NSCLC in which pembrolizumab is indicated for first-line treatment.

Trial Arms

NameTypeDescriptionInterventions
Group AExperimental
  • ALT-803 + Pembrolizumab
Group BActive Comparator
  • Pembrolizumab

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 4 NSCLC that: has not been treated with prior
             chemotherapy for metastatic disease and has high PD-L1 expression (ie, a TPS ≥ 50%),
             as determined by an FDA-approved test. Previous neoadjuvant/adjuvant chemotherapy is
             allowed if completed ≥ 6 months before diagnosis of metastatic disease.The subject's
             tumor must not harbor an EGFR sensitizing (activating) mutation or ALK translocation.
             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 and ALK
             translocation status in all subjects with non-squamous histologies AND for subjects in
             whom testing is clinically recommended. If either an EGFR sensitizing mutation of ALK
             translocation is detected, additional information regarding the mutation status of the
             other molecule 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 with
             non-squamous histologies will not be randomized until the EGFR mutation status and/or
             ALK translocation status is available in source documentation at the site. For
             patients enrolled who are known to have a tumor of predominantly squamous histology,
             molecular testing for EGFR and ALK translocation will not be required as this is not
             standard of care and is not part of current diagnostic guidelines.

          4. Life expectancy of ≥ 3 months.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. Have at least 1 measurable lesion of ≥ 1.0 cm. Confidential and Proprietary 6 ALT-803
             and Pembrolizumab for NSCLC Altor BioScience Clinical Trial Protocol: QUILT-2.023

          7. Must be willing to release tumor biopsy specimen used for diagnosis of metastatic
             NSCLC (if available) for additional exploratory tumor molecular profiling.

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

          9. 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.

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

         11. 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), 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. Subjects with a history of basal or squamous cell
             carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer, or
             those that have received curative therapy with no disease recurrence for ≥ 5 years,
             may be enrolled.

          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.

          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 Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR
Measure:Overall Survival (OS)
Time Frame:24 Months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:24 Months
Safety Issue:
Description:Defined by RECIST Version 1.1 based on BICR.
Measure:Disease-specific survival (DSS)
Time Frame:24 Months
Safety Issue:
Description:
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:PFS
Time Frame:24 Months
Safety Issue:
Description:Defined by irRC based on BICR.
Measure:Overall Response Rate (ORR)
Time Frame:24 Months
Safety Issue:
Description:Defined by irRC based on BICR.
Measure:Duration of Response (DOR)
Time Frame:24 Months
Safety Issue:
Description:Defined by irRC based on BICR.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Altor BioScience

Trial Keywords

  • Pembrolizumab
  • ALT-803
  • Non-Small Cell Lung Cancer
  • Immunotherapy

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