Non Small Cell Lung CancerPhase 2NCT04495153
CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC
A Phase 2 study testing Aglatimagene besadenovec in people with Non Small Cell Lung Cancer, run by Candel Therapeutics, Inc. at 14 sites in United States.
Trial summary
The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Aglatimagene besadenovec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 14 sitesUnited States
- Study dates
- 13 Oct 2020to Dec 2026
- Phase
- Phase 2
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
- Patients with Stage III/IV NSCLC on first line treatment with anti-PD-1/PD-L1 (ICI) +/- chemotherapy for their current stage of disease and fits into one of the following cohorts as determined by investigator, preferably as per RECIST 1.1: Cohort 1) have persistent but stable disease at least 18 weeks after starting ICI treatment, or Cohort 2) have radiographic progressive disease at least 18 weeks after starting ICI treatment
- RECIST evaluable disease including a lesion that is amenable to injection
- Able and willing to undergo a pre-treatment and on-treatment biopsies, if feasible
- ECOG Performance status of 0 or 1
- 18 years of age or older
- Granulocyte count (ANC) ≥ 1,000/mm3
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- Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)
- Platelets ≥ 75,000/mm3
- Total bilirubin ≤ 1.5 x upper limit of normal, except for patients with known Gilbert disease who must have total bilirubin ≤ 3 x upper limit of normal
- SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such that ICI can continue
- INR no more than 0.2 above upper limit of normal and aPTT not >1.2 x upper limit of normal, and value is acceptable for patient to undergo injection procedure. If on anti-coagulation, it must be clinically acceptable to hold anti-coagulation for the injection procedures per investigator discretion
- Serum creatinine < 2mg/dl and calculated creatinine clearance > 30ml/min
- Clinically stable and able to continue ICI for at least the 12-week treatment period
- Within 6 months of enrollment, no change of ICI therapy or prior interruptions of more than 4 weeks of current ICI
- Patients should not have received focal therapy (e.g., radiotherapy) at more than three different sites of disease within 12-months prior to enrollment
- Patients must give study specific informed consent prior to enrollment and any study specific procedures
Who cannot join
- Patients with a history of severe immune related adverse events related to ICI
- Patients who require ongoing therapy with disease-modifying antirheumatic drugs (DMARDs), immunomodulators or systemic immunosuppressive drugs including systemic corticosteroids (>10 mg prednisone per day or equivalent) - premedication for ICI or chemotherapy is allowed
- Patients with a history of active autoimmune disease requiring treatment in the past 2 years
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hepatitis, or psychiatric illness/social situations that would limit compliance with study requirements
- Women who are pregnant, lactating or intend to become pregnant during the study
- Patients who are known to be HIV positive
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- Patients with a history of hypersensitivity or allergic reactions to valacyclovir or acyclovir
- Patients with significant heart disease (New York Heart Association Functional Classification III or IV)
- Patients with continuous oxygen dependence >2L/min at rest
- Tumor impinging on a neurovascular structure such that inflammation in the site may put patient at risk of compromise as determined by the investigator
- Patients with uncontrolled brain metastases as per investigator
- Patients with liver metastases involving more than half of the liver
- Patients with known EGFR mutation, ALK fusion, or ROS1 fusion positive NSCLC, or that are receiving tyrosine kinase inhibitor (TKI) agents/ALK/ROS1 inhibitors
- Patients with known interstitial lung diseases (ILDs) requiring active therapy (Radiographic fibrosis not requiring therapy is allowed)
- Patients receiving vascular endothelial growth factor (VEGF) inhibitors (including bevacizumab, ramucirumab) within the past 2 months or five half-lives, whichever is longer
- Patients must have no concurrent malignancy requiring treatment (except squamous or basal cell skin cancers)
- Patients without contrast enhanced imaging at baseline or those with contraindication to the use of contrast.
- Patients who are pregnant, breastfeeding, or plan to become pregnant.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Maryland, Baltimore
Baltimore, Maryland, 21201
University of Chicago
Chicago, Illinois, 60637
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
UConn Health
Farmington, Connecticut, 06030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale University, Yale Cancer Center
New Haven, Connecticut, 06510
NYU Langone Health
New York, New York, 10016
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249
Virginia Commonwealth University
Richmond, Virginia, 23298
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients
The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have suboptimal response to ICI therapy.
Read the detailed description
This clinical trial evaluates the addition of CAN-2409 plus prodrug for stage III/IV NSCLC patients who are on standard of care first line ICI (anti-PD-1/PD-L1) but with evidence of suboptimal response (either disease progression or stable disease at time of study enrollment). CAN-2409 plus prodrug has been shown to increase the response rate to ICI in animal studies. Safety and tolerability of CAN-2409 plus prodrug has been demonstrated in clinical trials in over 950 patients with cancer, including cancers of the lung, pancreas, prostate, and brain. Initial proof of mechanism has been shown in non-small lung cancer, prostate cancer, high-grade glioma, and pancreatic cancer. The eligibility criterion in the current clinical trial is based on time on ICI and response status with cohorts as follows:
Cohort 1A and 1B: patients with stable disease radiographically at least 18 weeks after starting ICI treatment and who are clinically stable
Cohort 2A and 2B: patients with evidence of radiographic progression at least 18 weeks after starting ICI treatment but who are clinically stable.
Cohort 3, which is now closed for enrollment, was for patients who had evidence of radiographic progression at least 9 weeks after starting ICI but who were clinically stable.
The specific ICI treatment regimen is not specified to allow for different standard of care options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus chemotherapy, or atezolizumab/chemotherapy. In addition, it allows stage III patients after chemoradiation who may be on durvalumab as their standard of care. For example, a stage III patient may be eligible for cohort 2 if they have radiographic progression but are clinically stable 18 weeks after starting durvalumab.
The release of Version 05 of the protocol increased enrollment numbers into Cohorts 1 and 2 (from target n=32 evaluable to n=40 evaluable), while closing Cohort 3. In Amendment 6, cohort 1B and 2B were initiated to evaluate a 3-dose regimen of CAN-2409 + prodrug. Adjustments to the sample size extended the anticipated primary completion date for this trial.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Aglatimagene besadenovec
- Keywords
- Lung cancer, Immunotherapy, GMCI, AdV-tk, aglatimagene besadenovec, CAN-2409
- 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.
Aglatimagene besadenovecBiological
Also called CAN-2409, AdV-tk
Two courses (Cohort 1A and Cohort 2A) or three courses (Cohort 1B and Cohort 2B) of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). For Cohort 1B, the third course is optional. All patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Cohorts | Other | Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment
Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment
Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT) Receives: Biological: Aglatimagene besadenovec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)
Measured: 12 months
Safety graded by CTCAE version 5.0
Frequency of adverse events
Measured: 12 weeks
Secondary outcomes (5)
Biomarker Studies
Blood and tumor will be evaluated for changes in immune response before and after CAN-2409 + prodrug
Measured: 6 months
Overall Survival (OS)
Defined as time from date of first dose of CAN-2409 to death by any cause (OS-1). An additional OS will be defined as time from ICI treatment initiation to death due to any cause (OS-2).
Measured: 3 years
Progression Free Survival (PFS)
Defined as time from date of first dose of CAN-2409 to post-treatment progression or death by any cause (PFS-1). An additional PFS estimate will be calculated from ICI treatment initiation (PFS-2).
Measured: 3 years
Changes in patient-reported symptoms using the NSCLC-SAQ
Non-small Cell Lung Cancer Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.
Measured: 12 months
Response rate
Tumor Response as measured by iRECIST criteria
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start13 Oct 2020
- Primary completion31 Dec 2024
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study is a phase II prospective study to evaluate the safety and potential efficacy of CAN-2409 plus prodrug added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Candel Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- NYU Langone Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04495153
- Sponsor's protocol ID
- LuTK02
- Status last verified
- Aug 2025
- First submitted
- 24 Jul 2020
- Last updated
- 22 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Aggarwal C, Sterman D, Dwyer J, Alesi ER, Maldonado F, Mehra R, Bestvina C, Reisenauer J, Patel S, Ibrahim O, Eapen G, Guesdon W, Chung MWH, Duault C, Pichavant MR, Gnjatic S, Kim-Schulze S, Maecker HT, Diers AR, Guo Q, Nichols G, Manzanera A, Barone F, Tak PP. Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer. J Immunother Cancer. 2026 Sep 28;14(9):e015821. doi: 10.1136/jitc-2026-015821.
PubMed 42805763