Lung CancerPhase 1NCT06125197
Oncolytic Adenovirus TILT-123 With Pembrolizumab as Treatment for Refractory Non-Small Cell Lung Cancer
A Phase 1 study testing TILT-123 and KEYTRUDA® in people with Lung Cancer, run by TILT Biotherapeutics Ltd. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- TILT-123 and KEYTRUDA®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Jul 2024to 30 May 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 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
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- 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.
- ECOG/WHO performance score of 0-1 at screening.
- Life expectancy longer than 3 months.
Who cannot join
- 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.
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- 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.
- Has an active infection requiring systemic therapy.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Allergy to ingredients present in the investigational medicinal products (ingredients are listed in the protocol) ie. severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Known contraindications to pembrolizumab.
- Has had an allogenic tissue/solid organ transplant.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed.
- Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92658
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404
About this study
Official title: A Phase I Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab in Patients With Immune Checkpoint Inhibitor Refractory Non-Small Cell Lung Cancer
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
- Being tested
- TILT-123, KEYTRUDA®
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TILT-123Biological
Also called Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123)
Tumor necrosis factor alpha (TNFalpha) and Interleukin-2 (IL-2) coding oncolytic adenovirus TILT-123
KEYTRUDA®Biological
Also called pembrolizumab, pembrolizumab (MK-3475)
pembrolizumab, a monoclonal antibody binding PD-1
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: TILT-123; Biological: KEYTRUDA® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Phase
Incidence of DLT AEs in subjects with refractory NSCLC
Measured: 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.
Measured: Day 1 to Day 85
Secondary outcomes (1)
Dose Escalation Phase MTD
Determine the Maximum Tolerated Dose in patients with refractory NSCLC
Measured: Day 1 to Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2023
- Study start23 Jul 2024
- Primary completion30 Jan 2026 (estimated)
- Study completion30 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TILT Biotherapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06125197
- Sponsor's protocol ID
- Tilt-T610
- Other IDs
- MK-3475-E46, KEYNOTE-E46
- Status last verified
- Dec 2025
- First submitted
- 31 Oct 2023
- Last updated
- 23 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab in Patients With Immune Checkpoint Inhibitor Refractory Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06125197
- Acronym / sponsor ID
- Tilt-T610
- Conditions
- Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- TILT Biotherapeutics Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 23 Jul 2024 (actual)
- Primary completion
- 30 Jan 2026 (estimated)
- Study completion
- 30 May 2026 (estimated)
- First posted
- 9 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TILT-123 and Pembrolizumab | Experimental | Biological: TILT-123, Biological: KEYTRUDA®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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (23 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TILT-123Also: Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123)Tumor necrosis factor alpha (TNFalpha) and Interleukin-2 (IL-2) coding oncolytic adenovirus TILT-123 | Biological | TILT-123 and Pembrolizumab |
| KEYTRUDA®Also: pembrolizumab, pembrolizumab (MK-3475)pembrolizumab, a monoclonal antibody binding PD-1 | Biological | TILT-123 and Pembrolizumab |
Primary outcome
Dose Escalation Phase
Time frame: Day 1 to Day 85
Incidence of DLT AEs in subjects with refractory NSCLC
Incidence of Adverse Events
Time frame: Day 1 to Day 85
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.
1 secondary outcome
Dose Escalation Phase MTD
Time frame: Day 1 to Day 85
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TILT-123 and KEYTRUDA® in people with Lung Cancer, run by TILT Biotherapeutics Ltd. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation Phase (time frame: Day 1 to Day 85). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.