Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

University of California (UC) Davis

Status and phase: Not yet enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer Stage IIIC; Non-small Cell Lung Cancer Stage IV; Non-small Cell Lung Cancer Unresectable; Non-small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer

Treatments: Drug: Standard of Care; Drug: Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment.

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07250477

UCDCC323

Details and patient eligibility

About

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.

Full description

Participants will be randomized to an intervention arm or a standard of care (SOC) arm. Participants in the intervention arm will undergo pretreatment assessment with PROphet Clinical Benefit (CB) and the Cancer and Aging Research Group Toxicity Tool (CARG-TT); data from the assessments will be used to select systemic therapy, which can be any SOC treatment that incorporates a Programmed death-ligand 1 (PD-(L)1) antibody with or without chemotherapy and/or with or without Cytotoxic T-lymphocyte associated protein 4 (CTLA4) antibody. Participants in the SOC arm will undergo SOC biomarker assessment and subsequent selection of SOC systemic therapy. The primary endpoint is 12-month progression free survival (PFS). The findings will be stratified according to participant performance status and tumor PD-L1 score. The hypothesis is that risk-adapted, proteomic-guided systemic therapy will improve PFS among patients with previously untreated advanced NSCLC compared to SOC systemic therapy.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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).
• Stated ability and willingness to adhere to all protocol requirements while on study

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

Systemic immune checkpoint inhibitor (ICI)-based therapy informed by PROphet CB and CARG-TT

Experimental group

Treatment:

Drug: Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment.

Standard of Care

Active Comparator group

Description:

Standard of care (SOC) biomarker assessment and subsequent selection of SOC systemic therapy.

Treatment:

Drug: Standard of Care