The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2

Starting soon · Phase 2

Conditions studied: Non-small Cell Lung Cancer

In brief

This is a randomized trial evaluating the efficacy and safety of sequential dual-agent immunotherapy and risk-adapted radiotherapy for patients with locally advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score of at least 50%. Participants will be randomized between two dual-agent immunotherapy regimens: durvalumab + monalizumab versus durvalumab + oleclumab.

Key facts

Study ID: NCT07146230
Run by: Montefiore Medical Center
People needed: 52
Starts: 2026-09-01
Expected to finish: 2029-02-01
Last updated by the study team: 2026-06-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations, including follow-up.
Age > 18 years at time of study entry
Body weight ≥35 kg
Life expectancy of at least 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Previously untreated, pathologically proven NSCLC and one of the following stages:
American Joint Committee on Cancer (AJCC) version 8 Stage II disease, medically or technically unresectable
AJCC version 8 Stage III disease
Recurrent disease after curative-intent treatment for early-stage NSCLC, with current disease burden that would qualify as AJCC version 8 stage II-III
PD-L1 testing performed using an FDA-approved immunohistochemical assay and demonstrating tumor proportion score (TPS) of at least 50%.
Whole body PET/CT within 42 days prior to study entry demonstrating at least one hypermetabolic pulmonary lesion or thoracic lymph node.
MRI of the brain or head CT with contrast within 42 days prior to study entry.
PFTs within 42 days of study entry are recommended but not required.
Adequate normal organ and marrow function as defined below:
Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L Platelet count ≥75 × 109/L Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with Gilbert's syndrome.
Serum albumin ≥ 3.0 g/dL AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal Measured creatinine clearance >40 mL/min or Calculated creatinine clearance >40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
Males: (Weight in kg) x (140 - Age) ÷ (72 x serum creatinine in mg/dL)
Females: (Weight in kg) x (140 - Age) x 0.85 ÷ (72 x serum creatinine in mg/dL)

You may not qualify if…

Participation in another clinical study with an investigational product during the last 3 months
Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy, with these exceptions:
Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment on this study may be included after consultation with the Study Physician.
Any concurrent chemotherapy, Intraperitoneal (IP) chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
History of another primary malignancy except for
Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
History of leptomeningeal carcinomatosis
Prior radiotherapy that would preclude safe delivery of radiotherapy as specified in this study.
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first planned dose of IP.
History of allogenic organ transplantation.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
Patients with celiac disease controlled by diet alone
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of grade 3 or greater edema (e.g., peripheral, pulmonary)
History of venous thrombosis within the past 3 months prior to the planned first dose of study treatment. Note: Subjects with thrombosis due to mechanical obstruction by the tumor that is found incidentally and is asymptomatic and does not require therapy may be enrolled at the investigator's discretion and should be closely monitored.
Cardiac or peripheral vascular disease meeting any of the following criteria:
History of myocardial infarction in the prior 12 months

Where it is running

Montefiore Medical Center — The Bronx, New York, United States

Full record on ClinicalTrials.gov

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