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

NCT07146230 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2024-15810
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Immunotherapy; Radiotherapy; Patient reported outcomes; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Response rate observed using FDG-PET imaging

  Response rate will be assessed using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria prior to radiotherapy initiation. Response rate will be defined as a ≥ 30% decline in maximum standardized uptake value (SUV) without development of new disease sites. Response rates, which include partial metabolic responses and complete metabolic responses, will be presented as a count and percentage for each study arm. Participants who do not undergo FDG-PET after completion of induction immunotherapy (e.g., due to clinical disease progression, toxicity, or death) will be counted as non-responders.

  Following completion of two cycles of induction dual-agent immunotherapy; approximately 9 weeks

Secondary Outcomes (5)

• Response rates observed using Computed Tomography (CT)

  Following completion of two cycles of induction dual-agent immunotherapy; approximately 9 weeks

• Progression free survival (PFS)

  From randomization until the date of death, up to approximately 54 weeks

• Overall survival (OS) rates

  From randomization until the date of death, up to approximately 54 weeks

• Rates of disease progression during treatment

  Following completion of two cycles of induction dual-agent immunotherapy; approximately 9 weeks

• Physician-scored adverse events

  During study therapy; up to approximately 54 weeks

Study Arms (2)

Durvalumab + Monalizumab Arm

EXPERIMENTAL

Durvalumab 1500 mg IV and monalizumab 1500 mg IV on day 1 of a 28-day cycle for two cycles, followed by four weeks of risk adapted, dose-painted, radiotherapy, followed by durvalumab 1500 mg IV and monalizumab 1500 mg IV on day 1 of 28-day cycle for up to ten cycles.

Drug: Durvalumab; Drug: Monalizumab; Radiation: Radiotherapy

Durvalumab + Oleclumab Arm

EXPERIMENTAL

Durvalumab 1500 mg IV on day 1 and oleclumab 3000 mg IV on day 1 and 15 of a 28-day cycle for two cycles, followed by four weeks risk adapted, dose-painted radiotherapy, followed by durvalumab 1500 mg and oleclumab 3000 mg on day 1 of 28-day cycles for up to ten cycles.

Drug: Durvalumab; Drug: Oleclumab; Radiation: Radiotherapy

Interventions

Durvalumab DRUG

Durvalumab is a human mAb of the immunoglobulin G 1 kappa subclass that blocks the interaction of PD-L1 (but not PD-L2) with PD 1 on T cells and CD80 (B7.1) on immune cells.

Durvalumab + Monalizumab Arm; Durvalumab + Oleclumab Arm

Monalizumab DRUG

Monalizumab is a humanized mAb of the IgG4 subtype that specifically binds and inhibits Cluster of Differentiation 94 (CD94)/NK cell protein group 2 A(NKG2A).

Durvalumab + Monalizumab Arm

Oleclumab DRUG

Oleclumab is a human IgG1λ mAb that selectively binds to and inhibits the ectonucleotidase activity of CD73.

Durvalumab + Oleclumab Arm

Radiotherapy RADIATION

PET based dose painted radiotherapy. If these treatment techniques are not available for some reason treatment may be delivered using a sequential boost technique (2.75 Gy x 17 to the low-risk PTV followed by 2.75 Gy x 3 to the high-risk planning target volume).

Durvalumab + Monalizumab Arm; Durvalumab + Oleclumab Arm

Eligibility Criteria

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

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:

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:

Sponsors & Collaborators

• AstraZeneca: collaborator
• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

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  PMID: 19845652 BACKGROUND

• Paul S, Bodner WR, Garg M, Tang J, Ohri N. Cardiac Irradiation Predicts Activity Decline in Patients Receiving Concurrent Chemoradiation for Locally Advanced Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):597-601. doi: 10.1016/j.ijrobp.2020.05.042. Epub 2020 Jun 1.

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• Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis. 1974 Sep;27(7-8):365-75. doi: 10.1016/0021-9681(74)90015-0. No abstract available.

  PMID: 4612056 BACKGROUND

• Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, Almeida FD, Xiao Y, Ohri N, Brockway KD, Piper JW, Nelson AS. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):1164-71. doi: 10.1016/j.ijrobp.2010.12.055. Epub 2011 Apr 29.

  PMID: 21531085 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; monalizumab; Radiotherapy

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)

Therapeutics

Study Officials

• Nitin R Ohri, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nitin R Ohri, MD

CONTACT

718-405-8550; nitin.ohri@einsteinmed.edu

Akash Shah

CONTACT

7184058550; ashah1@montefiore.org

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: August 21, 2025
• First Posted: August 28, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)