Aglatimagene Besadenovec + Prodrug and Pembrolizumab vs Docetaxel for Stage IV Non-Squamous NSCLC Progressing on Pembrolizumab (AURORA) (LuTK03)

A Phase 3, Multicenter, Randomized, Controlled, Open-Label Clinical Trial of Aglatimagene Besadenovec (CAN-2409) Plus Prodrug and Pembrolizumab Versus Docetaxel for Stage IV Non-Squamous Non-Small Cell Lung Cancer Progressing on Pembrolizumab-based Treatment

This phase III trial compares the effect of the combination of aglatimagene besadenovec and pembrolizumab versus standard of care docetaxel chemotherapy for the treatment of stage IV non-squamous, non-small cell lung cancer. Aglatimagene besadenovec is a replication-deficient adenoviral vector encoding the herpes simplex virus thymidine kinase (HSV-tk) gene. When combined with an oral prodrug (valacyclovir), injection of aglatimagene induces targeted tumor cell death and stimulates a systemic immune response. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving aglatimagene with pembrolizumab is more effective at treating patients with stage IV non-squamous, non-small cell lung cancer than standard chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Non-squamous, Non-Small Cell Lung Cancer
• Intervention / Treatment: Biological: Aglatimagene Besadenovec; Drug: Valacyclovir; Biological: Pembrolizumab; Drug: Docetaxel

Detailed Description

PRIMARY OBJECTIVE:

I. To compare overall survival (OS) in participants previously treated with platinum-based chemotherapy and pembrolizumab-based immunotherapy for stage IV non-squamous, non-small cell lung cancer (NSCLC) randomized to pembrolizumab and aglatimagene plus prodrug (valacyclovir) versus standard of care docetaxel chemotherapy.

SECONDARY OBJECTIVES:

I. To compare patient-reported outcomes (PRO) between participants treated with aglatimagene besadenovec + prodrug in combination with pembrolizumab versus SoC docetaxel chemotherapy.

II. To evaluate the safety of aglatimagene besadenovec + prodrug in combination with pembrolizumab versus SoC docetaxel chemotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive two aglatimagene intratumoral injections followed by oral prodrug and pembrolizumab IV on study.

ARM 2: Patients receive docetaxel chemotherapy per standard of care on study.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • Principal Investigator: Daniel Sterman, MD
      • Contact: Daniel Sterman, MD; Phone Number: 212-263-8865; Email: Daniel.Sterman@nyulangone.org
      • Contact: NYU Langone Health ClinicalTrials.gov Administrators; Email: Ct.gov@nyulangone.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years, at the time of signing the informed consent.
2. Histologically confirmed metastatic Stage IV non-squamous NSCLC.

3. Measurable disease per RECIST v1.1 with at least 1 thoracic lesion amenable to intratumoral injection (e.g., pathological lymph node or lung lesion).

   Note: Able to be reached by bronchoscopy (including robotic bronchoscopy or flexible bronchoscopy with or without endobronchial ultrasound), or by percutaneous injection.

4. Documented radiographic progression observed in at least 3 consecutive scans or according to RECIST v1.1 criteria after a minimum of 12 weeks on continued pembrolizumab, determined by central review.

   Note: Participants on a pembrolizumab-based regimen should have achieved a best overall response (BOR) of at least SD (e.g., participants with a BOR of PD while on pembrolizumab are not eligible).

5. Prior treatment requirements:

   1. Must have received platinum-based chemotherapy in any line of therapy.
   2. May have received pembrolizumab therapy in combination with chemotherapy or sequentially. Note: The participant must be currently progressing on pembrolizumab or a pembrolizumab-based regimen.
6. ECOG performance status of 0 or 1 at screening.

7. Has adequate bone marrow function, defined as:

   1. Platelet count ≥ 75,000/mm3.
   2. Hemoglobin ≥ 9.0 g/dL (
   3. Absolute neutrophil count (ANC) ≥ 1500/mm3

8. Has adequate organ function, defined as: a) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×upper limit of normal (ULN); (≤ 5.0 × ULN if transferase elevation is due to liver metastases) AND b) Total bilirubin ≤ 1.5 × ULN (< 3.0 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases at baseline). c) Creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation). d) International normalized ratio (INR) < 1.5 without anticoagulants, INR < 3 if on prophylactic anticoagulation therapy.

   e) Prothrombin time (PT) and either partial thromboplastin (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

9. Completion of prior therapy with required washout and recovery:

   • Cytotoxic chemotherapy: > 14 days from the last dose.
   • Monoclonal antibodies (e.g., bevacizumab, ramucirumab): ≥ 5 half-lives or ≥ 42 days, whichever is longer.
   • Recovered to ≤ Grade 1 from prior therapy-related clinical toxicities (except alopecia and stable endocrine replacement).
10. Projected life expectancy ≥ 12 weeks (or 3 months) in the opinion of the Investigator.
11. Pregnancy test (for females of childbearing potential) negative at screening.
12. Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.

Exclusion Criteria:

Participants meeting any exclusion criteria for this trial will be disqualified from entering the study.

1. Has a known actionable genomic alteration, including EGFR, ALK, or ROS1 rearrangements, for which approved targeted therapy exists. Participants who are receiving or have previously received tyrosine kinase inhibitor (TKI) therapy targeting EGFR, ALK, or ROS1 are excluded.
2. Prior therapy with docetaxel either as monotherapy or in combination with other agents.
3. Prior treatment with CTLA-4 inhibitor (e.g., ipilimumab).
4. History of severe irAEs related to ICI.
5. Has a known history of active autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years is excluded. Note: Participants receiving physiologic corticosteroid replacement (e.g., ≤ 10 mg/day prednisone equivalent) are eligible.
6. History of hypersensitivity or allergic reactions to valacyclovir.
7. Active, uncontrolled, clinically significant bacterial, fungal, or viral infection, or any ongoing infection requiring systemic therapy.
8. Clinically active central nervous system (CNS) metastases or leptomeningeal disease. Evidence of new or progression of CNS confirmed by imaging during the study screening.
9. Persistently symptomatic bone metastases.
10. Has liver metastases involving more than half of the liver.
11. Prior radiotherapy within 2 weeks of the start of the study drug.
12. Has a known history of active interstitial lung diseases (ILD) (≥ grade 2) or noninfectious pneumonitis requiring active therapy, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at screening, or clinically severe pulmonary compromise due to intercurrent pulmonary illness and/or pulmonary disorder (e.g., severe chronic obstructive pulmonary disease, restrictive lung disease, etc.) requiring supplemental oxygen (>2L/min at rest) or any autoimmune, connective tissue or inflammatory disorders with active pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or any prior pneumonectomy.
13. Receiving or anticipated to receive investigational agents or has used an investigational device within 4 weeks prior to the first dose of study drug.
14. Ongoing clinically significant toxicity (> Grade 2 except alopecia), associated with prior treatment including systemic therapy, radiotherapy, or surgery.
15. Has a known history of Human Immunodeficiency Virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS)-related illness.
16. Has a known active or known prior history of Hepatitis B (HBV) infection (e.g., hepatitis B virus surface antigen [HBsAg] reactive or detectable quantitative levels of HBV DNA) or known active Hepatitis C (HCV) (e.g., hepatitis C virus RNA [quantitative] is detected).

17. Has an uncontrolled or significant heart disease, defined as:

    1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 470 msec (based on the average of Screening triplicate 12-lead electrocardiogram [ECG] determinations).
    2. Myocardial infarction or uncontrolled/unstable angina within 6 months before randomization.
    3. Congestive heart failure (CHF) (New York Heart Association [NYHA] Class II to IV) at Screening (see Appendix 12.3).
    4. Uncontrolled or significant cardiac arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication).
    5. NYHA Class III or IV Functional Classification.
    6. LVEF < 40% by ECHO or MUGA scan within 28 days before randomization.
    7. Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) within 28 days before randomization.

18. Has a concurrent malignancy requiring active systemic or local anti-cancer treatment except for the following:

    • Adequately treated non-melanoma skin cancer (squamous or basal cell cancers).
    • In situ cervical cancer that has been adequately treated.

    • Early-stage malignancies under active surveillance or observation only, including but not limited to:

      • Low-risk prostate cancer managed with active surveillance- Ductal carcinoma in situ of the breast managed with observation
19. Participants of childbearing potential, who are pregnant, lactating, or intend to become pregnant or father children during the study.
20. Any other significant physical and medical co-morbid conditions, including psychiatric conditions that, in the opinion of the Investigator, would impair study participation or cooperation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1:Continued pembrolizumab with two courses of Aglatimagene besadenovec plus prodrug; Patients continue to receive pembrolizumab with two courses of Aglatimagene besadenovec plus valacyclovir	Biological: Aglatimagene Besadenovec; via intratumoral injections into lung or lymph nodes at two timepoints; Drug: Valacyclovir; Oral, for14 days following each aglatimagene besadenovec injection; Biological: Pembrolizumab; every 3 weeks (Q3W) or every 6 weeks (Q6W)
Active Comparator: Arm 2: Docetaxel; Patients receive standard of care docetaxel	Drug: Docetaxel; every 21 days with standard premedication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To evaluate whether treatment with aglatimagene besadenovec (CAN-2409) plus valacyclovir and continued pembrolizumab improves overall survival (OS) compared to standard of care (SoC) docetaxel chemotherapy, in participants with Stage IV non-squamous non-small cell lung cancer (NSCLC) whose disease has progressed following prior pembrolizumab-based platinum chemoimmunotherapy	From date of randomization until date of death from any cause, assessed for a minimum of 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to meaningful deterioration based on the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score	Defined as the time from randomization until a definitive clinically meaningful worsening in symptoms or in NSCLC-SAQ total score. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.	Baseline to Week 12
Change from baseline of Total Score of NSCLC-SAQ at Week 12	NSCLC-SAQ Total Score after Week 12 compared to baseline. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.	Baseline to Week 12
Change from baseline of Global Health Status/QoL Score of EORTC-QLQ-30 at Week 12	EORTC-QLQ-30 Global Health Status/QoL Score after Week 12 compared to baseline. The lowest score possible is 0, and the highest score possible is 100. Higher score indicates less severe symptoms.	Baseline to Week 12
Frequency of Treatment Emergent Adverse Events (TEAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)	Treatment Emergent Adverse Events (TEAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)	Baseline to 120 days after last administered dose of study drug
Change from baseline in clinical laboratory parameters	Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics.	Baseline to 120 days after last administered dose of study drug

Collaborators and Investigators

• Sponsor: Candel Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): October 22, 2031
• Study Completion (Estimated): October 22, 2031

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Docetaxel; NSCLC; Non-Small Cell Lung Cancer; Pembrolizumab; Aglatimagene besadenovec; CAN-2409; Non-Squamous
• 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; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Taxoids; Cyclodecanes; Diterpenes; Acyclovir; Docetaxel; Valacyclovir; pembrolizumab
• Other Study ID Numbers: CAN-2409-LuTK03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No