TU2218 + Pembrolizumab for Solid Tumors

Recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with advanced solid tumors, aiming to determine if adding TU2218 to Pembrolizumab (an immunotherapy drug) is safe and effective. The trial focuses on cancers such as biliary tract, head and neck, and colorectal cancers. Participants should have solid tumors unresponsive to standard treatments, be able to take pills, and have measurable tumors. This trial may suit individuals whose cancer has not improved with previous therapies and who need another treatment option. 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 combination therapy.

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.

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

Research shows that Pembrolizumab, a component of this trial treatment, is generally well-tolerated and effective for various solid tumors, such as lung cancer and melanoma. It aids the body's immune system in fighting cancer cells. In past studies, patients tolerated Pembrolizumab well, with common side effects including tiredness and mild skin reactions.

Regarding TU2218, studies have shown that when combined with Pembrolizumab, it controlled the disease in 80% of cases for certain cancers, like Biliary Tract Cancer. This suggests that the combination of TU2218 and Pembrolizumab could be well-tolerated. However, since TU2218 remains under study, its safety is not fully known.

Overall, this combination treatment is in early-phase trials designed to assess safety. These trials help identify possible side effects and the optimal dose. Researchers closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TU2218 combined with Pembrolizumab because this duo offers a fresh approach to tackling various solid tumors, including biliary tract cancer, head and neck squamous cell carcinoma, and colorectal cancer. Unlike traditional treatments that might rely solely on chemotherapy or radiation, TU2218 is administered orally and works alongside Pembrolizumab, an established immunotherapy drug, to boost the body's immune response against cancer cells. This combination targets tumors with a unique mechanism, potentially offering more effective and targeted results. Additionally, the innovative oral delivery method of TU2218 alongside Pembrolizumab's intravenous administration could improve patient convenience and compliance.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

This trial will evaluate the combination of TU2218 and Pembrolizumab (KEYTRUDA®) for treating various solid tumors. Studies have shown that Pembrolizumab effectively treats cancers such as non-small cell lung cancer and melanoma, helping patients live longer. It is also used for head and neck cancer. Previous research demonstrated that 80% of patients experienced disease control when TU2218 was combined with Pembrolizumab, particularly in certain cancers like biliary tract cancer. TU2218 blocks pathways that allow cancer cells to grow. This trial aims to leverage the strengths of both treatments to combat advanced solid tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

TU2218

Principal Investigator

TiumBio Co., Ltd.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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, 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) 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]

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, 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) 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) 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05784688

NCT05784688 | Study of TU2218 in Combination With ... This study consists of phase 1b and 2a to evaluate safety, Pharmacokinetics, and efficacy of TU2218 in combination with Pembrolizumab in patients with advanced ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05784688/study-of-tu2218-in-combination-with-keytrudarpembrolizumab-in-patients-with-advanced-solid-tumors

Study of TU2218 in Combination With KEYTRUDA ... This study consists of phase 1b and 2a to evaluate safety, Pharmacokinetics, and efficacy of TU2218 in combination with Pembrolizumab in ...

3. withpower.com withpower.com/trial/phase-2-neoplasms-2-2023-0eafe

TU2218 + Pembrolizumab for Solid Tumors Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates and ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT484138

Phase 2 trial of TU2218, TGFβ-RI, and VEGF-R2 dual ... In particular, 80% DCR was observed in TU2218 195mg/day in combination with Pembrolizumab. The trial was expanded to the specific cancer types, Biliary Tract ...

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT05784688

Study of TU2218 in Combination With KEYTRUDA ... ESMO 2024 (Poster) - 1014P - Phase Ib trial results of safety, pharmacokinetics and pharmacodynamics of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in ...