Non-small Cell Lung Cancer Stage IIICPhase 2NCT07250477
Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer
A Phase 2 study testing Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment. in people with Non-small Cell Lung Cancer Stage IIIC and Non-small Cell Lung Cancer Stage IV, run by University of California, Davis at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Stage IIIC, Non-small Cell Lung Cancer Stage IV, Non Small Cell Lung Cancer
- What is being tested?
- Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Jan 2026to Dec 2036
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Enloe Health Regional Cancer Center
Chico, California, 95926
Ranjan Pathak, MD, 530-332-7300, ranjan.pathak@enloe.org
Ranjan Pathak, MD
- Recruiting
Rideout Cancer Center
Marysville, California, 95901
Hoa Nguyen, MD, 530-749-4400, nguyenh01@ah.org
Hoa Nguyen, MD
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Surbhi Singhal, MD, 916-734-3772, susinghal@health.ucdavis.edu
Surbhi Singhal, MD
- Recruiting
Tahoe Forest Cancer Center
Truckee, California, 96161
Thomas Semrad, MD, 530-582-6450, tsemrad@tfhd.com
Thomas Semrad, MD
About this study
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.
Read the 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
- Being tested
- Systemic (ICI)-based therapy informed by the PROphet CB assay and the CARG-TT assessment., Standard of Care
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Standard of CareDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Systemic immune checkpoint inhibitor (ICI)-based therapy informed by PROphet CB and CARG-TT | Experimental | Not described Receives: 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. Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
- 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
Measured: 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
Time from the start of treatment to the date of treatment discontinuation or death due to any cause, whichever occurs first
Measured: 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.
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.
Measured: 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.
Overall survival (OS) defined as the time from the start of treatment to death due to any cause or 60 months, whichever occurs first.
Measured: Up to 60 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2025
- Study start30 Jan 2026
- Primary completionMay 2036 (estimated)
- Study completionDec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer Stage IIICStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Surbhi Singhal, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07250477
- Sponsor's protocol ID
- UCDCC323
- Other IDs
- NCI-2026-00133
- Status last verified
- Aug 2026
- First submitted
- 18 Nov 2025
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No