TU2218 + Pembrolizumab for Solid Tumors

Recruiting at 10 trial locations

Overseen By TiumBio Global http://www.tiumbio.com/en/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: TiumBio Co., Ltd.

Must not be taking: Anticoagulants, Immunosuppressants, Corticosteroids, others

Disqualifiers: Cardiac disease, Brain metastasis, Autoimmune, 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: 11

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This study consists of phase 1b and 2a to evaluate safety, Pharmacokinetics, and efficacy of TU2218 in combination with Pembrolizumab in patients with advanced solid tumors.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, such as strong inhibitors of specific enzymes and gastric pH elevating agents, at least 8 days before and during the study. Additionally, no other anti-cancer treatments are allowed for a specified period before starting the trial. It's best to discuss your current medications with the study team to see if they are affected.

What data supports the effectiveness of the drug pembrolizumab for treating solid tumors?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates and reducing tumor size. It works by helping the immune system attack cancer cells more effectively. ^{1 2 3 4 5}

Is the combination of TU2218 and Pembrolizumab safe for treating solid tumors?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash. More serious immune-related side effects, like inflammation of the lungs (pneumonitis) and type 1 diabetes, can occur but are less common. ^{1 2 4 6 7}

What makes the drug TU2218 + Pembrolizumab unique for treating solid tumors?

The combination of TU2218 and Pembrolizumab is unique because it involves Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, which has shown effectiveness in various solid tumors. This combination may offer a novel approach by potentially enhancing the immune response against tumors compared to using Pembrolizumab alone. ^{1 2 3 8 9}

Research Team

TU2218

Principal Investigator

TiumBio Co., Ltd.

Eligibility Criteria

Adults with advanced solid tumors who have adequate organ function, can comply with the study protocol, and are not pregnant or breastfeeding. They must have measurable disease, a life expectancy of at least 12 weeks, and for certain cohorts, be naive to specific treatments or have progressed after them. Participants should not be on conflicting medications or have conditions that could affect their safety in the trial.

Inclusion Criteria

My liver and kidney functions are normal.

My advanced cancer cannot be surgically removed and has not responded to or tolerated standard treatments.

QTcF interval ≤470 msec on screening ECG

Exclusion Criteria

I have a history of severe bleeding or risk factors for it.

I have a moderate or severe problem with my heart valve.

I have received a transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Participants receive TU2218 orally and KEYTRUDA® intravenously daily for two weeks followed by one week to determine RP2DC

3 weeks

3 visits (in-person)

Phase 2a Treatment

Participants receive TU2218 orally BID for 2 weeks followed by 1 week of rest in 3-week cycles and KEYTRUDA® intravenously every 3 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Pembrolizumab
• TU2218

Trial Overview The trial is testing TU2218 combined with Pembrolizumab to assess its safety and effectiveness against advanced solid tumors. Phase 1b aims to find the right dose while phase 2a focuses on how well it works for selected tumor types.

Participant Groups

Group I: Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in Head and Neck Squamous Cell Carcinoma (HNSCC) Experimental Treatment 1 Intervention

TU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)

Group II: Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in ColoRectal Cancer (CRC) Experimental Treatment 1 Intervention

TU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)

Group III: Phase 2a: TU2218 + KEYTRUDA® (Pembrolizumab) in Biliary Tract Cancer (BTC) Experimental Treatment 1 Intervention

TU2218 + KEYTRUDA® (Pembrolizumab) administered, orally BID, for 2 weeks followed by 1 week of rest in 3-week cycles for TU2218 and intravenous 200mg once every 3 weeks for KEYTRUDA® (Pembrolizumab)

Group IV: Phase 1b: TU2218 + KEYTRUDA® (Pembrolizumab) in solid tumor Experimental Treatment 1 Intervention

TU2218 orally and KEYTRUDA® (Pembrolizumab) intravenously administered daily for two weeks followed by one week to determine RP2DC.

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?

TiumBio Co., Ltd.

Lead Sponsor

Trials

4

Recruited

510+

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

Findings from Research

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, 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 (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]

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) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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]

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) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]