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

NCT02839265 | Completed Phase 2 Results DMC

• 1 other identifier: 2015-5267
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Dose Limiting Toxicities (DLTs)

  30 days

• Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)

  Up to 27 months post-randomization

• Radiographic Response Rate Based on PET Response Criteria in Solid Tumors (PERCIST)

  Up to 27 months post-randomization

• Overall Survival (OS)

  From date of treatment to date of death, up to 5 years

Study Arms (1)

SBRT + FLT3 Ligand Immunotherapy

EXPERIMENTAL

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); Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

FLT3 Ligand Therapy (CDX-301) DRUG

See Arm 1 descriptions

SBRT + FLT3 Ligand Immunotherapy

Stereotactic Body Radiotherapy (SBRT) RADIATION

See Arm 1 descriptions

Also known as: Stereotactic Ablative Radiotherapy (SABR)

SBRT + FLT3 Ligand Immunotherapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Celldex Therapeutics: collaborator
• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Nitin Ohri
• Organization: Montefiore Medical Center

nitin.ohri@einsteinmed.edu

718-920-7750

Study Officials

• Nitin Ohri, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: July 20, 2016
• Study Start: July 1, 2016
• Primary Completion: October 5, 2022
• Study Completion: November 22, 2024
• Last Updated: April 28, 2026
• Results First Posted: June 6, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)