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.
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.
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
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
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
10. An active infection requiring systemic IV therapy.
11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
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.