Non-squamous, Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, Non-Squamous, CAN-2409, Aglatimagene besadenovec, Pembrolizumab, Docetaxel, Non-Small Cell Lung Cancer
Brief summary
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.
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.
Interventions
BIOLOGICALAglatimagene Besadenovec
via intratumoral injections into lung or lymph nodes at two timepoints
DRUGValacyclovir
Oral, for14 days following each aglatimagene besadenovec injection
BIOLOGICALPembrolizumab
every 3 weeks (Q3W) or every 6 weeks (Q6W)
DRUGDocetaxel
every 21 days with standard premedication
Sponsors
Candel Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization until date of death from any cause, assessed for a minimum of 24 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to meaningful deterioration based on the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score | Baseline to Week 12 | 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. |
| Change from baseline of Total Score of NSCLC-SAQ at Week 12 | Baseline to 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. |
| Change from baseline of Global Health Status/QoL Score of EORTC-QLQ-30 at Week 12 | Baseline to 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. |
| Frequency of 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 | Treatment Emergent Adverse Events (TEAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) |
| Change from baseline in clinical laboratory parameters | Baseline to 120 days after last administered dose of study drug | Observed values and changes from baseline for continuous clinical laboratory parameters will be summarized at each scheduled timepoint using descriptive statistics. |
Countries
United States
Outcome results
None listed