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.
This is a phase 3, open-label, 4-cohort study (3 randomized cohorts and 1 single-arm cohort). Participants enrolled in each cohort will be treated as detailed below. Each study cohort will be analyzed separately. 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.
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
• Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease must not be candidates for treatment with surgical resection or chemoradiation.
• 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.
• For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as determined by an FDA-approved test.
• 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.
• ECOG performance status of 0 or 1.
• Measurable tumor lesions according to RECIST 1.1.
• 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.
⁃ Must be willing to provide blood samples prior to the start of treatment on this study for exploratory tumor molecular profiling analysis.
⁃ 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.
⁃ 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 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.
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines
• Histologically-confirmed stage III or IV NSCLC disease. Participants with stage III disease must not be candidates for treatment with surgical resection or definitive chemoradiation.
• ECOG performance status of 0 to 2.
• Measurable tumor lesions according to 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 participants of childbearing potential and non-sterile males. Female participants of childbearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and nonsterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables. two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.