TILT-123 + Pembrolizumab for Lung Cancer

Recruiting at 1 trial location

Overseen By TILT Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TILT Biotherapeutics Ltd.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune, Cardiac, Hepatic, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments: TILT-123 (an oncolytic adenovirus coding for TNFa and IL2) and Pembrolizumab (also known as KEYTRUDA, an immune checkpoint inhibitor), for individuals with non-small cell lung cancer unresponsive to other immune-based therapies. The trial aims to assess the safety of this combination and determine the optimal dose. It targets those with lung cancer that cannot be cured with available treatments and whose cancer is worsening after immune therapy. Participants will receive varying doses of TILT-123 alongside Pembrolizumab to evaluate their body's response. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like systemic steroids or have had recent anti-cancer therapy. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of TILT-123 and Pembrolizumab is under study for safety. Early studies with ovarian cancer patients indicate that the treatment is generally well-tolerated. Most side effects were mild to moderate, such as tiredness and fever. However, a few reports noted more serious side effects, though these were rare.

The FDA has already approved Pembrolizumab for treating other cancers, indicating its safety for those uses. TILT-123 is a newer treatment still undergoing testing, so safety information remains limited. The current trial is in its early stages and aims to determine the safest dose. As a result, safety is still under investigation, and more data will clarify how well people tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

TILT-123 paired with Pembrolizumab is unique because it combines an innovative viral therapy with an existing immunotherapy. While most treatments for lung cancer, like chemotherapy or radiation, aim to directly kill cancer cells, TILT-123 works differently by using a virus to boost the body’s immune response against cancer. This enhanced immune activation might improve the efficacy of Pembrolizumab, which already helps the immune system recognize and attack cancer cells. Researchers are excited about this combination because it could offer a more powerful weapon against lung cancer by enhancing the immune system's ability to fight the disease.

What evidence suggests that TILT-123 and Pembrolizumab could be effective for lung cancer?

Research shows that TILT-123, a type of virus, attacks cancer cells and boosts the immune system with the help of two proteins, TNFα and IL-2. In this trial, participants will receive a combination of TILT-123 and pembrolizumab, a drug that aids the immune system in attacking cancer. Studies have found that combining TILT-123 with pembrolizumab can improve outcomes for people with non-small cell lung cancer. Early results suggest this combination helps the body fight cancer cells previously resistant to immune therapies. Overall, using TILT-123 with pembrolizumab appears promising for treating lung cancer by enhancing the immune system's ability to combat the disease. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer that's not responding to immune checkpoint inhibitors. They need a tumor big enough for safe biopsy, measurable disease per RECIST 1.1, and good organ function shown by specific blood counts (WBCs >3.0, ANC ≥1500/µL, Platelets ≥100000/µL, Hemoglobin ≥9.0 g/dL).

Inclusion Criteria

Specimens must be collected within 10 days prior to the start of study treatment

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

Life expectancy longer than 3 months

Exclusion Criteria

I have or had lung inflammation that needed steroids.

I am currently being treated for an infection.

I have had radiotherapy within the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple administrations of TILT-123 and Pembrolizumab with dose escalation based on safety evaluations

12 weeks

Multiple visits for dose administration and safety evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• TILT-123

Trial Overview The trial tests TILT-123 (an oncolytic adenovirus) combined with Pembrolizumab in patients whose lung cancer hasn't improved with standard immunotherapy. It's an early-phase study where researchers gradually increase the dose to find the safest level.

How Is the Trial Designed?

Group I: TILT-123 and Pembrolizumab Experimental Treatment 2 Interventions

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.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

TILT Biotherapeutics Ltd.

Lead Sponsor

Trials

5

Recruited

100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 411 patients with non-small cell lung cancer (NSCLC), 33% showed no PD-L1 expression, 38% had low expression, and 29% exhibited high expression, indicating a significant variability in PD-L1 status among patients.

The study found that PD-L1 positivity was linked to factors such as male sex, smoking history, higher tumor grade, and specific histologic types, suggesting that these characteristics may influence the effectiveness of pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience. Takeda, M., Kasai, T., Naito, M., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1. nature.com nature.com/articles/s41467-025-56482-w

The oncolytic adenovirus TILT-123 with pembrolizumab in ... Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06125197?cond=%20Adenovirus%20%20Cancer&

Oncolytic Adenovirus TILT-123 With Pembrolizumab as ... 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 ...

3. tiltbio.com tiltbio.com/userassets/uploads/2024/04/TILT-123-data-at-AACR-2024.pdf

TILT-123 in Combination with KEYTRUDA® ( ... TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), is designed to enhance the efficacy of ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5562

PROTA: A phase I clinical trial combining an oncolytic ... A phase I clinical trial combining an oncolytic adenovirus encoding for TNFa and IL-2 with pembrolizumab for the treatment of platinum-resistant or -refractory ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/30/17/3715/747277/Safety-Efficacy-and-Biological-Data-of-T-Cell

Safety, Efficacy, and Biological Data of T-Cell–Enabling ... This study demonstrates the safety of TILT-123 as a cancer therapy and lays the groundwork for future studies of TILT-123 in specific ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05271318

NCT05271318 | Oncolytic Adenovirus Coding for TNFa ... This is an open-label, phase 1/2, dose-escalation, multicenter and multinational trial evaluating the safety of oncolytic adenovirus TILT-123 in combination ...