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

NCT ID: NCT07250477

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2036-12-31

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Pretreatment 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

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

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

Standard 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.

Interventions

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

Pretreatment 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.

Intervention Type: DRUG

Standard of Care

Standard 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Surbhi Singhal, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Countries

United States

Central Contacts

Surbhi Singhal, MD

Role: CONTACT

susinghal@health.ucdavis.edu

(916) 734-3772

Facility Contacts

Surbhi Singhal, MD

Role: primary

susinghal@health.ucdavis.edu

916-734-3772

Other Identifiers

UCDCC323

Identifier Type: -

Identifier Source: org_study_id