TU2218 + Pembrolizumab for Solid Tumors

Recruiting in Palo Alto (17 mi)

+10 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: TiumBio Co., Ltd.

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

Disqualifiers: Cardiac disease, Brain metastasis, Autoimmune, others

No Placebo Group

Breakthrough Therapy

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}

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.

Trial 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

Participant Groups

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.

Group I: Phase 2a: TU2218 + KEYTRUDA® 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® 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® 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® 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NEXT Oncology San Antonio, TX

Hope Cancer Center Tyler, TX

Medical Oncology Spokane, WA

Who Is Running the Clinical Trial?

TiumBio Co., Ltd. Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

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] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

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] On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021] On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.

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

Pembrolizumab: first global approval. [2021] Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022] Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023] Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023] Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.

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

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021] The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.