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Non Small Cell Lung CancerPhase 1/2FLT3NCT04491084

FLT3 Ligand, CD40 Agonist Antibody, and Stereotactic Radiotherapy

A Phase 1/2 study testing FLT3 Ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT in people with Non Small Cell Lung Cancer and Lung Cancer, run by Albert Einstein College of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to test a new way of treating the most common form of lung cancer. The investigators are testing a combination of radiotherapy with two new forms of immunotherapy. This study is testing the safety and effectiveness of this treatment approach as compared to standard treatment options. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer, Lung Cancer
What is being tested?
FLT3 Ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
1 Jan 2021to 18 Aug 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven NSCLC, not classically deemed to be amenable to curative therapy based on disease extent at the time of diagnosis or disease progression after the initial diagnosis
  • Age ≥ 18 years
  • Prior treatment with at least two lines of systemic therapy for advanced NSCLC, including one line of platinum-based combination chemotherapy
  • Treatment with concurrent chemotherapy and immunotherapy can count as two lines of therapy for the purposes of study eligibility.
  • Radiological assessment within 21 days prior to study entry demonstrating measurable disease that includes at least one pulmonary or extrapulmonary 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
  • ECOG performance status 0-2
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  • Both men and women enrolled in this trial must agree to use adequate birth control measures during the trial and for at least 90 days after last receipt of study therapy. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
  • The following laboratory results, within 21 days prior to first study drug administration (Arm 1) or within 21 days prior to study registration (Arm 2):
  • 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 OR creatinine clearance (by Cockcroft-Gault formula) > 60 mL/min AST and ALT ≤ 2.5 x ULN Total bilirubin ≤ 2.0 x ULN (except patients with Gilbert's syndrome, who must have a total bilirubin ≤ 3.0 mg/dL)
  • -Negative SARS-CoV-2 (COVID-19) PCR test. COVID-19 testing may be repeated periodically based on institutional policies and must be repeated for any subject with unexplained signs (e.g., imaging findings, fever) or symptoms (e.g., anosmia) concerning for COVID-19 infection or with recent known exposure to COVID-19.

Who cannot join

  • Prior therapy with any anti-CD40 antibody or FLT3 ligand
  • Less than 21 days between registration and the last receipt of chemotherapy, targeted cancer therapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or major surgery.
  • 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. -Patients without a history of brain metastases and without symptoms suggestive of brain metastasis do not require staging imaging of the brain prior to study enrollment.
  • Known mutation/amplification in FLT3
  • Ongoing or recent (within 21 days prior to study entry) use of high dose oral corticosteroids (≥ 2 mg of dexamethasone daily or equivalent) or inhaled corticosteroids. Intranasal and/or intraarticular corticosteroid use is permitted.
  • History of non-infectious pneumonitis or any ongoing pneumonitis
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  • History of allogeneic organ transplant or active autoimmune disease
  • Other active malignancy for which systemic therapy (excluding hormonal therapy for breast or prostate cancer) is indicated.
  • History of myocardial infarction, cerebral vascular accident, thrombosis, or pulmonary embolus within 12 months prior to study registration.
  • 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
  • Active infection requiring systemic therapy, known HIV infection, or positive test for hepatitis B surface antigen or hepatitis C (antibody screen and if positive confirmed by RNA analysis). If positive results are not indicative of a true active or chronic infection, the patient can be enrolled after discussion with, and agreement by, the Principal Investigator.
  • Receipt of a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  • Subjects who are not ambulatory or ambulate using a walker are not eligible for the objective activity monitoring component of this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: FLT3 Ligand (CDX-301), CD40 Agonist Antibody (CDX-1140), and Stereotactic Radiotherapy Versus Standard Therapy for Advanced Non-small Cell Lung Cancer: A Phase I/II Randomized Trial

The purpose of this study is to test a new way of treating the most common form of lung cancer. The investigators are testing a combination of radiotherapy with two new forms of immunotherapy. This study is testing the safety and effectiveness of this treatment approach as compared to standard treatment options.

Read the detailed description

This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus standard care (Arm 2). Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional "cycles" of FLT3 ligand (CDX-301) anti-CD40 antibody (CDX-1140), and SBRT at later time points. Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians. All subjects will be followed closely for treatment-related toxicities. Whole-body PET/CT and CT imaging will be performed prior to study entry, and restaging CT will be performed every 8 weeks thereafter.

In the phase I component of this study, subjects will be randomized between study arms until 6 subjects have been randomized to Arm 1. Study accrual will then be halted until 8 weeks after the last study subject begins treatment.

If the pre-specified safety criteria are achieved in the Phase I portion of this study, the study will proceed to phase II. The total sample size (Phase I and Phase II) will be 46 subjects. All 46 subjects will be included in efficacy analyses.

If the pre-specified safety criteria are not achieved in the Phase I portion of this study, the investigators and Celldex will review safety data from this trial as well as other trials using CDX-301 and CDX-1140 and determine if the experimental treatment regimen should be altered (e.g., by reducing the CDX-1140 dose). The study protocol would be amended accordingly, and Phase I component with the new treatment regimen would be added.

Being tested
FLT3 Ligand (CDX-301), anti-CD40 antibody (CDX-1140), SBRT
Keywords
CDX-301, CDX-1140
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FLT3 Ligand (CDX-301)Drug

    Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.

  • anti-CD40 antibody (CDX-1140)Biological

    CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells

  • SBRTRadiation

    For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.

Study groups in NCT04491084
Study groupRoleWhat they receive
FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRTExperimentalSubjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional "cycles" of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.
Receives: Drug: FLT3 Ligand (CDX-301); Biological: anti-CD40 antibody (CDX-1140); Radiation: SBRT
Standard careActive comparatorSubjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.
Receives: Radiation: SBRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:

    Death

    Any ≥ Grade 3 non-hematological toxicity, with the following exceptions:

    Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities

    Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however:

    Any Grade 4

    Measured: up to 8 weeks after initiation of study therapy

  2. Phase II: Progression-free Survival (PFS) Duration

    Measured: defined as time from study registration until disease progression (scored using iRECIST) or death, whichever comes first up to 51 weeks.

Secondary outcomes (5)

  1. Overall Survival (OS) Duration

    Length of time that patient survives from time of study registration

    Measured: From date of registration until the date of death from any cause, assessed up to 2 years

  2. Radiographic Responses Using Descriptive Statistics

    The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.

    Measured: From date of registration, assessed up to 4 months

  3. Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)

    Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning

    Measured: 1 year

  4. Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)

    Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.

    Measured: 1 year

  5. Daily Step Count Using Descriptive Statistics

    Average daily step counts

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2020
  2. Study start1 Jan 2021
  3. Primary completion18 Aug 2022
  4. Study completion18 Aug 2022

Why it stopped: Low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus standard care (Arm 2).
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04491084
Sponsor's protocol ID
2020-11868
Acronym
FLT3
Status last verified
Feb 2024
First submitted
21 Jul 2020
Last updated
28 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing FLT3 Ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT in people with Non Small Cell Lung Cancer and Lung Cancer, run by Albert Einstein College of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Dose-limiting Toxicity (DLT), Defined as Follows: (time frame: up to 8 weeks after initiation of study therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04491084.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.

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