This is a phase 2, pragmatic, 1:1 randomized, open-label study that evaluates risk-adapted, proteomic-guided systemic therapy to improve 12-month progression free survival (PFS) among patients with previously untreated advanced non-small cell lung cancer.
Participants must have histologically confirmed non-small cell lung cancer that is metastatic or unresectable (stage IIIC or IV), deemed appropriate to receive standard of care immune checkpoint inhibitor-based therapy given with palliative intent.
Age ≥18 years at the time of consent.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥50%).
Ability to understand and willingness to sign the informed consent form (ICF).
Tumor with known sensitizing alteration in ALK, EGFR, HER2, MET exon 14, NTRK, RET, or ROS1.
Medical comorbidities precluding immune checkpoint inhibitor-based therapy per treating investgator's discretion.
Previous systemic therapy for metastatic Stage IIIC or IV NSCLC. Patients who previously completed systemic therapy for early stage or locally advanced NSCLC ≥ 80 days prior to trial registration are eligible for inclusion.
Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on study
Parallel
Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment.
DrugPretreatment assessment with PROphet CB and CARG-TT, which will be used to determine which first-line systemic treatment participants in the intervention arm receive. Systemic treatment will be pre-determined by the trial, according to the results from PROphet CB and CARG-TT.
Standard of Care
DrugStandard of care (SOC) biomarker testing followed by first-line treatment with either anti-PD(L)1 Immune checkpoint inhibitor (ICI) monotherapy or anti-PD(L)1 ICI + chemotherapy.
The primary objective is to evaluate 12-month progression free survival (PFS) of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy
Progression free survival (PFS) at 12 months, defined as progression assessed per investigator using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause at 12 months (± 28 days) from start of treatment.
To evaluate treatment-related adverse events of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy.
* Grade ≥3 treatment-related adverse events from chemotherapy classified and graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 * Grade ≥2 treatment-related adverse events from immune checkpoint inhibitors classified and graded per NCI CTCAE v5.0 * Number of dose delays, dose reductions, and/or dose discontinuations for treatment-related adverse event * Initiation and dose of systemic steroids for possible immune-related adverse event
To evaluate time to treatment discontinuation of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy
Time from the start of treatment to the date of treatment discontinuation or death due to any cause, whichever occurs first
To evaluate overall PFS of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy.
Overall progression free survival (PFS) defined as the time from the start of treatment to the first date of the progression (any progression assessed per investigator using RECIST v1.1) or death due to any cause, whichever occurs first.
To evaluate overall survival (OS) among participants treated with systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy.
Overall survival (OS) defined as the time from the start of treatment to death due to any cause or 60 months, whichever occurs first.
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University of California, Davis
Lead sponsor
National Cancer Institute (NCI)
Collaborator
