Oncolytic Adenovirus TILT-123 With Pembrolizumab as Treatment for Refractory Non-Small Cell Lung Cancer

NCT06125197 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: Tilt-T610MK-3475-E46KEYNOTE-E46
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, Phase 1, dose escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab in patients with immune checkpoint inhibitor refractory non-small cell lung cancer.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Dose Escalation Phase

  Incidence of DLT AEs in subjects with refractory NSCLC

  Day 1 to Day 85

• Incidence of Adverse Events

  Determine the safety and tolerability of the combination of TILT-123 and Pembrolizumab in patients with refractory non-small cell lung cancer by evaluating the number, frequency, and severity of adverse events using CTCAE v 5.0.

  Day 1 to Day 85

Secondary Outcomes (1)

• Dose Escalation Phase MTD

  Day 1 to Day 85

Study Arms (1)

TILT-123 and Pembrolizumab

EXPERIMENTAL

Patients will receive multiple administrations of TILT-123 and Pembrolizumab. Escalation to the next dose of TILT-123 will occur when the safety data has been evaluated for patients in the preceding dose level.

Biological: TILT-123; Biological: KEYTRUDA®

Interventions

TILT-123 BIOLOGICAL

Tumor necrosis factor alpha (TNFalpha) and Interleukin-2 (IL-2) coding oncolytic adenovirus TILT-123

Also known as: Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123)

TILT-123 and Pembrolizumab

KEYTRUDA® BIOLOGICAL

pembrolizumab, a monoclonal antibody binding PD-1

Also known as: pembrolizumab, pembrolizumab (MK-3475)

TILT-123 and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed NSCLC cancer which cannot be treated with curative intent with available therapies and is refractory to or progressing after anti-PD(L)1 immunotherapy or immunotherapies.
• At least one tumor lesion (\>15 mm or bigger) must be available for biopsy that in the opinion of the investigator, is accessible to repeated biopsies without major safety concerns.
• The patient must have disease evaluable per RECIST 1.1
• Have adequate organ function as defined in the following values below. Specimens must be collected within 10 days prior to the start of study treatment.
• Hematological laboratory values
• Absolute neutrophil count (ANC): ≥1500/µL
• Platelets: ≥ 100 000/µL
• Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months.
• Leukocytes (WBC) \> 3.0
• Renal laboratory values
• GFR: \>45 ml/min (Cockcroft-Gault formula).
• Hepatic laboratory values
• Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN (excluding patients with Gilbert's disease)
• AST (SGOT) and ALT (SGPT): ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• Patients must be willing to use adequate forms of contraception from screening, during the trial, and for a minimum of 120 days after end of treatment.

You may not qualify if:

• Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) and inhaled and topical treatments are not considered a form of systemic treatment and are allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Treated with any anti-cancer therapy within 30 days prior to the first virus injection.
• Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Treated with a prior radiotherapy, including for palliative purposes, within 2 weeks of start of study treatment (before or after).
• Treated with a prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), cerebral stroke, unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.
• History of myocardial infarction or cerebral stroke within the previous 12 months before screening or is not sufficiently recovered from an older infarction or cerebral stroke.
• History of severe hepatic dysfunction.
• History of Hepatitis B (defined as HBsAg reactive), Hepatitis C (defined as HCV RNA \[qualitative\] is detected) or HIV. No testing for Hepatitis B, Hepatitis C and HIV is required unless mandated by a local health authority.
• History of coagulation disorder.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Female patients who are pregnant, breastfeeding or intend to become pregnant. Women of child bearing potential who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis.

Sponsors & Collaborators

• TILT Biotherapeutics Ltd.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658, United States

Location

UCLA Jonsson Comprehensive Cancer Center

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: November 9, 2023
• Study Start: July 23, 2024
• Primary Completion: January 30, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (2)