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

Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Systemic immune checkpoint inhibitor (ICI)-based therapy informed by PROphet CB and CARG-TT
  • Drug: 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.
Active Comparator
Standard of Care
Standard of care (SOC) biomarker assessment and subsequent selection of SOC systemic therapy.
  • 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.

Recruiting Locations

Enloe Health Regional Cancer Center
Chico, California 95926
Contact:
Ranjan Pathak, MD
530-332-7300
ranjan.pathak@enloe.org

Rideout Cancer Center
Marysville, California 95901
Contact:
Hoa Nguyen, MD
530-749-4400
nguyenh01@ah.org

University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
Contact:
Surbhi Singhal, MD
916-734-3772
susinghal@health.ucdavis.edu

Tahoe Forest Cancer Center
Truckee, California 96161
Contact:
Thomas Semrad, MD
530-582-6450
tsemrad@tfhd.com

More Details

Status
Recruiting
Sponsor
University of California, Davis

Study Contact

Office of Clinical Research
(916) 734-3772
OCRReferral@health.ucdavis.edu

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.