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

NCT07250477 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UCDCC323NCI-2026-00133
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months.

Secondary Outcomes (4)

• To evaluate treatment-related adverse events of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy.

  3, 6, 9, and 12 months

• To evaluate time to treatment discontinuation of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy

  Up to 12 months

• To evaluate overall PFS of systemic therapy informed by PROphet CB and CARG-TT (intervention arm) versus standard of care systemic therapy.

  Up to 60 months.

• 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.

  Up to 60 months.

Study Arms (2)

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

EXPERIMENTAL

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

Standard of Care

ACTIVE COMPARATOR

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

Drug: Standard of Care

Interventions

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

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

Standard of Care 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.

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on study

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• University of California, Davis: lead

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Surbhi Singhal, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Surbhi Singhal, MD

CONTACT

(916) 734-3772; susinghal@health.ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 26, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): May 1, 2036
• Study Completion (Estimated): December 1, 2036
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)