FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer (FLT3)

Based on promising data from our laboratory demonstrating synergy between ablative local radiotherapy and FLT3 ligand immunotherapy in murine NSCLC models, investigators are performing a phase II study combining FLT3L immunotherapy and SBRT for patients with advanced NSCLC that has progressed following standard systemic therapy. All patients will receive daily subcutaneous injections of CDX-301 (75 µg/kg) for 5 days, beginning on the first day of SBRT. SBRT will be delivered to a single pulmonary or extrapulmonary lesion. The SBRT regimen will depend on the size and location of the target lesion. The primary endpoint will be progression-free survival at 4 months, defined using immune-related response criteria (irRC).

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: FLT3 Ligand Therapy (CDX-301); Radiation: Stereotactic Body Radiotherapy (SBRT)

Detailed Description

Primary Objective

• To explore the efficacy of combining stereotactic body radiotherapy (SBRT) with FLT3 ligand immunotherapy for advanced non-small cell lung cancer (NSCLC).

Secondary Objectives

• To establish the feasibility and safety of combining SBRT with FLT3 ligand immunotherapy for advanced NSCLC.
• To quantify and evaluate potential surrogate outcomes for clinical efficacy of this treatment approach, including radiographic responses, immunologic responses, and circulating tumor cell levels.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• AJCC stage 3 or 4 histologically proven NSCLC not amenable to curative therapy
• Age >= 18 years
• Prior treatment with at least one standard chemotherapy regimen or targeted agent prior to enrollment
• Radiological assessment within 21 days prior to study entry demonstrating measurable disease that includes at least one pulmonary lesion . 1 cm in greatest dimension that would be amenable to SBRT and at least one measurable lesion that would be outside of the SBRT treatment fields
• History/physical examination within 30 days prior to registration
• ECOG performance status 0-2
• Signed, written informed consent

Exclusion Criteria:

• Less than 21 days between registration and the last receipt of chemotherapy, biotherapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or major surgery. Prior receipt of immunomodulatory therapy (eg: nivolumab) is permitted, as long as there has been a 21 day washout period following the most recent treatment.
• Untreated central nervous system metastases. Patients with a history of brain metastases must have had no CNS-directed therapy within the past 60 days and radiological assessment within 30 days of study entry demonstrating a lack of progressive CNS disease
• Ongoing or recent (within 21 days prior to study entry) use of high dose oral corticosteroids (.2 mg of dexamethasone daily or equivalent). Intranasal and/or inhaled corticosteroid use is permitted.
• Any unresolved CTCAE grade >2 toxicity from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study therapy (eg, hearing loss)may be enrolled after discussion with the principal investigators.
• History of allogeneic organ transplant or autoimmune disease
• Active malignancy, other than NSCLC, for which systemic therapy is indicated. History of adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy asides from hormonal therapy, adequately treated stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for >= 5 years is permitted.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by the treating physicians

• The following laboratory results, within 10 days of first study drug administration:

  • Hemoglobin . 9.0 g/dL, Absolute neutrophil count . 1.5 x 109/L, Platelet count . 100 x 109/L
  • Serum creatinine . 1.5 x ULN and creatinine clearance (by Cockcroft-Gault formula) < 60 mL/min
• Women of child bearing potential: positive pregnancy test (serum)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SBRT + FLT3 Ligand Immunotherapy; Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301); Daily subcutaneous injections of CDX-301 (75 ug/kg) will be administered for 5 days, beginning on the first day of SBRT.; Additional cycles of SBRT (to distinct lesions) and CDX-301 may be administered every 2-4 months to subjects who demonstrate evidence of clinical benefit (lack of treatment-related toxicity and no disease progression).; Study therapy will be discontinued in cases of treatment-related toxicity or disease progression.

Drug: FLT3 Ligand Therapy (CDX-301); See Arm 1 descriptions; Radiation: Stereotactic Body Radiotherapy (SBRT); See Arm 1 descriptions; Other Names: Stereotactic Ablative Radiotherapy (SABR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	The primary endpoint is progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after initiation of study therapy.	4 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	The number of participants with evidence of DLTs will be tabulated. For the purposes of this study, a DLT will be defined as any grade 3-5 treatment-emergent adverse event toxicity, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and occurring within 30 days after treatment with SBRT in combination with FLT3 ligand therapy (after the first treatment cycle). Asymptomatic laboratory abnormalities (eg: leukocytosis) that do not require intervention will not be counted as DLTs. For subjects who receive more than one "cycle" of SBRT and FLT3 ligand, only adverse events that occur after the first cycle will be scored as potential DLTs.	30 days
Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)	Radiographic Response will be scored using RECIST V1.1 criteria based on 1st post-treatment imaging to quantify objective measures of change in tumor burden. RECIST uses a max of 10 target lesions per patient to determine when tumors in cancer patients improve, stay the same, or worsen during treatment. RECIST will be used to quantify the percentage of patients demonstrating Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), as follows: CR - resolution of all target lesions to background levels PR - at least 30% decrease in sum of diameters of target lesions (noting baseline diameters) SD - neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD (noting smallest sum on study) PD - at least 20% increase in sum of diameters of target lesions (noting smallest sum on study); absolute increase of 5mm must be demonstrated; >=1 new lesion is considered PD If no CT/PET at a specific timepoint = "Not Evaluable"	Up to 27 months post-randomization
Radiographic Response Rate Based on PET Response Criteria in Solid Tumors (PERCIST)	Radiographic Response will be scored using PERCIST criteria based on the first PET imaging done. PERCIST is a set of rules that define when tumors in cancer patients improve, stay the same, or worsen during treatment, based on imaging data. PERCIST criteria will be used to quantify the percentage of patients demonstrating Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), Stable Metabolic Disease (SMD), Progressive Metabolic Disease (PMD), or Not Evaluable (NE) as follows: CMR - complete resolution of 18F-FDG uptake, disappearance of all target lesions to background levels, no new 18F-FDG lesions PMR - reduction of a minimum of 30% in target measurable tumor 18F-FDG SUL peak, no increase >30% in all lesions; no new lesions SMD - no CMR, PMR or PMD; no new lesions PMD - >30% increase in 18F-FDG peak; OR visible increase in extent of tumor uptake; OR new 18F-FDG lesions If CT/PET was not done at a specific timepoint, result will be considered "Not Evaluable"	Up to 27 months post-randomization
Overall Survival (OS)	Overall survival (OS) is defined as the percentage of patients alive at 5 years post-randomization. Data of subjects without a death record will be censored on the last known survival date.	From date of treatment to date of death, up to 5 years

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Celldex Therapeutics
• Investigators: Principal Investigator: Nitin Ohri, MD, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): October 5, 2022
• Study Completion (Actual): November 22, 2024

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (Estimated): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 2015-5267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO