A Study Evaluating Neoadjuvant Chemoimmunotherapy With Immunosensitizing Radiation for Borderline Resectable Non-Small Cell Lung Cancer

NCT06800339 | Recruiting Phase 1 DMC

• 1 other identifier: HP-00112115
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this research study is to find out if adding radiation prior to chemoimmunotherapy and surgery is effective for people with non-small cell lung cancer (NSCLC) who have the potential for surgery. Standard of Care Chemoimmunotherapy: For this study, standard of care chemotherapy will be used. This means this is the type of chemotherapy that is normal for your cancer. In addition to the chemotherapy, you will also receive the immunotherapy drug, nivolumab. This will be administered intravenously once every 3 weeks for up to 3 cycles (i.e. 9 weeks of total systemic therapy), prior to surgical resection assessment. This combination is made up of the chemotherapy drugs carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine, and the immunotherapy drug is nivolumab. The chemotherapy is used to kill cancer cells, and the immunotherapy enables your immune system to attack cancer cells. Stereotactic Body Radiation Therapy (SBRT) SBRT is when radiation is delivered at higher doses over a smaller period of time. For this study, you will receive three doses of radiation delivered every other day, for three total days. The final dose of radiation will happen within 7 days of starting chemoimmunotherapy. You will be followed for up to 100 days following your last chemoimmunotherapy dose to monitor for potential side effects. Following this you will continue with your standard follow up with your doctor. During the standard follow-up time, study staff will review your charts to see if there have been any new updates with your cancer following treatment so they can tell how this treatment affects how long patients live and whether it helps avoid recurrence of the cancer.

Conditions

Non-Small Cell Lung Cancer

Keywords

Radiation Treatment; SBRT; ChemoImmunotherapy

Outcome Measures

Primary Outcomes (1)

• Tolerability of Adding Sub-ablative, Immunosensitizing, Radiotherapy to Standard of Care Neoadjuvant Chemoimmunotherapy

  Evaluate the tolerability of adding sub-ablative, immunosensitizing, radiotherapy to standard of care neoadjuvant chemoimmunotherapy prior to surgery for resectable NSCLC, measured by the rate of DLTs from time of neoadjuvant therapy initiation to start of definitive therapy (either surgery or chemoimmunotherapy initiation).

  20 weeks post initiation of neoadjuvant therapy

Secondary Outcomes (4)

• Number of adverse events assessment by CTCAE v5.0 that are related to treatment

  20-22 weeks post initiation of neoadjuvant therapy

• Pathologic Complete Response Rate (pCR)

  20-22 weeks post initiation of neoadjuvant therapy

• Major Pathologic Response Rate (MPR)

  20-22 weeks post initiation of neoadjuvant therapy

• Measure rate of definitive resection

  1 year post completion of accrual

Study Arms (1)

SBRT+Chemoimmunotherapy +/-Surgery

EXPERIMENTAL

Standard of care chemotherapy along with nivolumab. Nivolumab will be infused every 3 weeks for up to 3 cycles. Chemotherapy options include: carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine. Concurrently patient will receive 3 fractions of SBRT. Patient will then be evaluated for possible surgical resection.

Drug: Nivolumab; Drug: Chemotherapy; Radiation: SBRT; Procedure: Surgical Resection

Interventions

Nivolumab DRUG

This will be administered intravenously once every 3 weeks for up to 3 cycles (i.e. 9 weeks of total systemic therapy)

SBRT+Chemoimmunotherapy +/-Surgery

Chemotherapy DRUG

Chemotherapy options include: carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine

SBRT+Chemoimmunotherapy +/-Surgery

SBRT RADIATION

Three fractions of radiation delivered every other day, for three total days. The final dose of radiation will happen within 7 days of starting chemoimmunotherapy

SBRT+Chemoimmunotherapy +/-Surgery

Surgical Resection PROCEDURE

Post treatment patient will be evaluated for surgical resection

SBRT+Chemoimmunotherapy +/-Surgery

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to18 years at time of study entry
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Participants with histologically confirmed stage II-IIIC(N3) NSCLC (per the 8th International Association for the Study of Lung Cancer) with disease that is considered borderline resectable prior to initiation of RT or systemic therapy.

You may not qualify if:

• Subject cases must be reviewed in a multidisciplinary thoracic tumor board setting prior to enrollment to allow for adequate discussion regarding the potential for resection.
• Participants must have a tumor tissue sample available for biomarker testing, including next-generation sequencing to confirm EGFR/ALK status. Assessment of EGFR/ALK status may be performed locally through a CLIA approved laboratory testing method.
• a. Tissue source may be a formalin fixed paraffin block (FFPE) of a previous tumor biopsy sample. Source of biomarker testing may be obtained from archived tissue if adequate or from a new biopsy, if needed and clinically indicated
• Absence of major associated pathologies that increase the surgery risk to an unacceptable level
• Pulmonary function capacity (eg. FVC, FEV1, TLC, and DLCO) capable of tolerating proposed lung resection according to surgeon.
• Adequate normal organ and marrow function defined below:
• Platelet count greater than or equal to100,000/mm3
• Hemoglobin greater than or equal to 8 g/dL
• Absolute neutrophil count (ANC) greater than or equal to 1000/mm3
• Creatinine less than or equal to 1.5 x ULN or creatinine clearance (CrCl) greater than or equal to 40 mL/min
• Total bilirubin less than or equal to 1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL)
• AST, ALT, Alkaline phosphatase less than or equal to 3 x ULN per local testing
• Subjects are deemed capable of giving informed consent and must have signed and dated an IRB approved written informed consent form. This written consent must be obtained before the performance of any protocol related procedures that are not part of normal standard of care.
• Women of childbearing potential (WOCBP) must have negative serum or urine pregnancy testing within 30 days of study start.
• Presence of metastatic (Stage IV) disease, including malignancy pleural effusions.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (4)

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

RECRUITING

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Upper Chesapeake- Kaufman Cancer Center

Bel Air, Maryland, 21014, United States

RECRUITING

Baltimore Washington Medical Center- Tate Cancer Center

Glen Burnie, Maryland, 21061, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Drug Therapy

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Central Study Contacts

Matthew Ferris, MD

CONTACT

410-328-6080; matthew.ferris@umm.edu

Caitlin Eggleston, MPH

CONTACT

410-328-7586; caitlineggleston@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: January 30, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)