Purpose

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 inhibitors (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is an oncolytic viral immunotherapy 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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. 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 2. RECIST evaluable disease including a lesion that is amenable to injection 3. Able and willing to undergo a pre-treatment and on-treatment biopsies, if feasible 4. ECOG Performance status of 0 or 1 5. 18 years of age or older 6. Granulocyte count (ANC) ≥ 1,000/mm3 7. Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion) 8. Platelets ≥ 75,000/mm3 9. 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 10. SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such that ICI can continue 11. 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 12. Serum creatinine < 2mg/dl and calculated creatinine clearance > 30ml/min 13. Clinically stable and able to continue ICI for at least the 12-week treatment period 14. Patients must give study specific informed consent prior to enrollment and any study specific procedures

Exclusion Criteria

  1. Patients with a history of severe hypersensitivity reaction to ICI 2. 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 3. Patients with a history of active autoimmune disease requiring treatment in the past 2 years 4. 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 5. Women who are pregnant, lactating or intend to become pregnant during the study 6. Patients who are known to be HIV positive 7. Patients with a history of hypersensitivity or allergic reactions to valacyclovir or acyclovir 8. Patients with significant heart disease (New York Heart Association Functional Classification III or IV) 9. Patients with continuous oxygen dependence >2L/min at rest 10. Tumor impinging on a neurovascular structure such that inflammation in the site may put patient at risk of compromise as determined by the investigator 11. Patients with uncontrolled brain metastases as per investigator 12. Patients with liver metastases involving more than half of the liver 13. Patients with known EGFR mutation, ALK fusion, or ROS1 fusion positive NSCLC, or that are receiving tyrosine kinase inhibitor (TKI) agents/ALK/ROS1 inhibitors 14. Patients with known interstitial lung diseases (ILDs) requiring active therapy (Radiographic fibrosis not requiring therapy is allowed) 15. Patients receiving vascular endothelial growth factor (VEGF) inhibitors (including bevacizumab, ramucirumab) within the past 2 months or five half-lives, whichever is longer 16. Patients must have no concurrent malignancy requiring treatment (except squamous or basal cell skin cancers)

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention 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
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Cohorts
Cohort 1 - persistent but stable disease at least 18 weeks after starting ICI treatment Cohort 2 - 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)
  • Biological: Aglatimagene besadenovec
    Two courses of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). Patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.
    Other names:
    • CAN-2409
    • AdV-tk

Recruiting Locations

University of Maryland, Baltimore
Baltimore, Maryland 21201
Contact:
Maha Khalil
410-328-5009
mkhalil@umm.edu

More Details

Status
Recruiting
Sponsor
Candel Therapeutics, Inc.

Study Contact

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 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 1 is for patients with stable disease radiographically at least 18 weeks after starting ICI treatment and are clinically stable. Cohort 2 is for 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. Adjustments to the sample size extended the anticipated primary completion date for this trial.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.