TU2218 + Checkpoint Inhibitors for Solid Tumors

Recruiting at 4 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, NSAIDs, Steroids, others

Disqualifiers: Heart disease, Infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TU2218 for individuals with advanced solid tumors, which are cancers forming in solid organs or tissues. The study aims to determine a safe dose of TU2218 and evaluate its effectiveness against these tumors. Some participants will take TU2218 alone, while others will receive it with an anti-PD-1 antibody, such as Pembrolizumab (Keytruda), which aids the immune system in fighting cancer. Ideal candidates for this trial have advanced solid tumors that have not responded to standard treatments. As a Phase 1 trial, this research focuses on understanding how TU2218 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires a washout period of 4 weeks for any biologic material and a minimum of 5 half-lives for any chemotherapy before starting treatment. You must also stop using certain medications like strong inhibitors of specific enzymes and gastric pH elevating agents at least 8 days before the study. If you are on chronic systemic steroids or other immunosuppressive medications, you may need to stop them as well.

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

Research has shown that TU2218, a drug tested for advanced solid tumors, is generally safe and well-tolerated. In earlier studies, when combined with pembrolizumab (a type of cancer drug), TU2218 did not cause major side effects, and patients tolerated the treatment well. This suggests that TU2218 might be safe to use alone or with other cancer drugs. However, as this trial is in the early stages, further research is needed to confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

TU2218 is unique because it targets solid tumors through a novel mechanism, potentially offering a fresh approach compared to existing treatments like chemotherapy and radiation. Unlike typical treatments, TU2218 can be paired with anti-PD-1 antibodies, potentially boosting the immune system's ability to fight cancer cells. This combination could enhance the effectiveness of immunotherapy, a promising area in cancer treatment. Additionally, TU2218 is administered orally, which might improve patient compliance and convenience compared to traditional intravenous therapies. Researchers are excited about these possibilities, hoping TU2218 could offer a new and effective option for patients with solid tumors.

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

Research shows that TU2218 may effectively treat advanced solid tumors. In this trial, some participants will receive TU2218 alone, which targets proteins involved in tumor growth and has shown good tolerance. Other participants will receive TU2218 combined with pembrolizumab, an anti-PD-1 antibody that aids the immune system in fighting cancer. Initial results suggest that this combination may help shrink tumors. The therapy potentially blocks the pathways tumors use to grow and evade the immune system. These findings offer hope for TU2218's potential in cancer treatment. ^{1 2 4 5 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 where standard therapy has failed or no effective standard exists. Participants must have adequate organ function, not be pregnant, and agree to use contraception. Exclusions include serious medical conditions, brain metastases, heart issues within the last 6 months, active infections including hepatitis B/C and HIV, history of severe bleeding or autoimmune diseases (with some exceptions), and inability to stop certain medications.

Inclusion Criteria

Life expectancy ≥12 weeks as judged by the Investigator

I have waited long enough after my last cancer treatment and any side effects are mild.

My liver and kidney functions meet the required levels.

Exclusion Criteria

I do not have any serious infections, including active hepatitis B or C, or HIV/AIDS.

I had heart or aortic surgery less than 6 months ago.

I haven't taken high-dose aspirin or certain blood thinners in the last 10 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Escalating doses of TU2218 administered alone and in combination with anti-PD-1 antibody for up to 21-day cycles to determine the Maximum Tolerated Dose (MTD)

6 weeks

Multiple visits per cycle

Phase 2 Treatment

TU2218 administered at the recommended Phase 2 dose (RP2D) alone and in combination with anti-PD-1 antibody to evaluate antitumor activity

24 weeks

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anti-PD-1 antibody
• TU2218

Trial Overview The trial is testing TU2218 alone (Part A) and in combination with an Anti-PD-1 antibody (Part B). It aims to find a safe dose for TU2218 (Phase 1) and assess its effectiveness against tumors at that dose (Phase 2). Patients are monitored for how their bodies handle the drug(s) and any signs of tumor shrinkage.

How Is the Trial Designed?

Group I: TU2218 Phase 2a Experimental Treatment 1 Intervention

TU2218 at a RP2D orally administered daily for two weeks followed by on week of rest for up to 21-day cycles

Group II: TU2218 Phase 1a Experimental Treatment 1 Intervention

Escalating doses of TU2218 orally administered daily for two weeks followed by one week of rest for up to 21-day cycles

Group III: TU2218 Food Effect Experimental Treatment 1 Intervention

TU2218 orally administered at a one dose level below MTD under fasting condition on -Day 2, followed by the same dose orally administered with meals on -Day 1 and then continued under fasted condition for two weeks followed by one week of rest for up to 21-day cycles

Group IV: TU2218 + Anti-PD-1 antibody Phase 2b Experimental Treatment 2 Interventions

TU2218 at a RP2DC in combination with anti-PD-1 antibody up to 21-day cycles

Group V: TU2218 + Anti-PD-1 antibody Phase 1b Experimental Treatment 2 Interventions

Escalating doses of TU2218 in combination with anti-PD-1 antibody up to 21-day cycles

Who Is Running the Clinical Trial?

TiumBio Co., Ltd.

Lead Sponsor

Trials

4

Recruited

510+

Published Research Related to This Trial

Immune checkpoint blockade, using monoclonal antibodies against CTLA-4 and PD-1/PD-L1, has significantly improved treatment outcomes for patients with advanced solid organ tumors, leading to long-lasting responses.

Despite its effectiveness, only a small percentage of patients experience meaningful benefits from these therapies, highlighting the need for better understanding of tumor characteristics and patient profiles to optimize treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response. Navani, V., Graves, MC., Bowden, NA., et al.[2021]

Immune checkpoint inhibitors are promising immunomodulatory agents that help reactivate immune cells to fight tumors, showing significant effectiveness in treating solid cancers like melanoma and non-small cell lung cancer.

Numerous clinical studies are currently investigating the benefits of these inhibitors across various cancer types, with a particular focus on their application in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. Gaynor, N., Crown, J., Collins, DM.[2022]

Older adults with solid tumors generally benefit from immune checkpoint inhibitors just as much as younger patients, and they tolerate these treatments well.

However, when older patients receive combination therapies that may increase toxicity, the benefits can be diminished, highlighting the need for careful patient selection and geriatric assessments to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for older patients with cancer. Araujo Vargas, TP., Al-Humiqani, A., Giffoni De Mello Morais Mata, D., et al.[2023]

Nivolumab, an anti-PD-1 monoclonal antibody, has significantly improved treatment outcomes for advanced cancers like lung cancer, renal cancer, and melanoma, promoting long-lasting anti-tumor immunity.

Despite its effectiveness, nivolumab monotherapy fails in 60-70% of patients, but combining it with other therapies, such as chemotherapy or CTLA-4 inhibitors, has been shown to enhance its efficacy and overcome resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy. Abedi Kiasari, B., Abbasi, A., Ghasemi Darestani, N., et al.[2022]

A study involving 448 patients with advanced cancers showed that immune checkpoint inhibitors, like anti-PD-1 and anti-CTLA4 therapies, are safe and well tolerated across different age groups, including those aged 75 and older.

Older patients (≥75 years) experienced fewer endocrine toxicities compared to younger patients, while they had a higher incidence of dermatological toxicities, indicating that age does not significantly increase the risk of severe adverse effects from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of age on the toxicity of immune checkpoint inhibition. Samani, A., Zhang, S., Spiers, L., et al.[2023]

Three patients developed uveal effusion, a condition affecting the eye, after starting anti-PD-1 and anti-PD-L1 monoclonal antibody therapy for cancer, highlighting a potential adverse effect of these immunotherapies.

The uveal effusion resolved in most cases after stopping the therapy, suggesting that while these treatments can be effective for cancer, they may also cause significant inflammatory side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uveal Effusion After Immune Checkpoint Inhibitor Therapy. Thomas, M., Armenti, ST., Ayres, MB., et al.[2022]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

Cancer immunotherapy, particularly through the use of immune checkpoint inhibitors like ipilimumab, has shown promising survival benefits in melanoma, with early trials indicating good tolerability and meaningful response rates across various cancer types.

Targeting inhibitory receptors on T cells can potentially overcome tumor-induced immune dysfunction, and combining different checkpoint inhibitors or integrating them with other therapies may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer immunology - development of novel anti-cancer therapies. Rothschild, SI., Thommen, DS., Moersig, W., et al.[2022]

Immune checkpoint inhibitors, specifically targeting CTLA-4 and PD-1, have been developed to enhance T-lymphocyte activity against cancer, leading to durable responses in various cancer types.

Pembrolizumab, an anti-PD-1 antibody, has been approved by the FDA and is now a key component of cancer treatment, although further research is needed to optimize its use and identify effective biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1) receptor pathway. Momtaz, P., Postow, MA.[2022]

Combination immunotherapies, such as PD-1 and CTLA-4 blockade, show promising results in treating non-small cell lung cancer (NSCLC), potentially improving outcomes compared to single-agent therapies.

Early clinical trials indicate that these combination therapies can be administered safely without significantly increasing toxicity, but further research is necessary to assess long-term safety, efficacy, and optimal patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Immunotherapy in Non-small Cell Lung Cancer. Marmarelis, ME., Aggarwal, C.[2022]

In the phase 3 MYSTIC trial involving 1118 patients with metastatic non-small cell lung cancer, durvalumab did not significantly improve overall survival compared to chemotherapy, nor did the combination of durvalumab and tremelimumab show better outcomes than chemotherapy for patients with high PD-L1 expression.

However, patients with a blood tumor mutational burden (bTMB) of 20 or more mutations per megabase experienced significantly improved overall survival with durvalumab plus tremelimumab, suggesting that bTMB may be a useful biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. Rizvi, NA., Cho, BC., Reinmuth, N., et al.[2021]

In a study of 85 patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer treated with immune checkpoint inhibitors (ICIs), a higher number of tumor infiltrating lymphocytes (TILs) was significantly associated with better treatment responses and survival outcomes.

The research found that patients with a high number of TILs had a response rate of 70.6% and significantly improved progression-free survival and overall survival compared to those with low TILs, suggesting that TIL count could serve as a predictive biomarker for ICI efficacy in MSI-H mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes. Loupakis, F., Depetris, I., Biason, P., et al.[2022]

Immune checkpoint inhibitors like ipilimumab, nivolumab, and pembrolizumab commonly cause skin-related side effects, which are often the first adverse events to appear during treatment, highlighting the need for prompt recognition and management.

This review provides practical guidance for healthcare professionals on identifying and treating these skin adverse events, based on data from clinical trials and real patient case studies, aiming to improve patient care and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective. Thebeau, M., Rubin, K., Hofmann, M., et al.[2018]

In a review of 19 trials involving 5404 participants, it was found that 4-10% of patients treated with PD-(L)1 inhibitors showed responses even after being classified as having disease progression, highlighting the unique efficacy of these immune checkpoint inhibitors.

The study suggests that traditional RECIST criteria are inadequate for evaluating responses to PD-(L)1 inhibitors, recommending the use of immune-related response criteria and advising that treatment should continue beyond initial progression until confirmed by a second evaluation at least 4 weeks later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonconventional patterns of benefit of solid tumors treated with PD-(L)1 inhibitors: a systematic review. Abdel-Rahman, O.[2018]

In a large study of 48,782 cancer cases, PD-L1 expression was more commonly found in immune cells than in tumor cells, and there was a strong correlation between PD-L1 expression and other biomarkers like CD274 gene amplification, microsatellite instability (MSI), and tumor mutational burden (TMB).

Over half of the cases (50.3%) tested positive for at least one biomarker related to immunotherapy response, highlighting the potential for personalized treatment strategies, particularly for the PD-L1+/TMB+ subset, which may respond best to immunotherapy, though further clinical trials are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pan-cancer analysis of PD-L1 immunohistochemistry and gene amplification, tumor mutation burden and microsatellite instability in 48,782 cases. Huang, RSP., Haberberger, J., Severson, E., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2613

Phase 1 trial of TU2218, TGFβ-RI and VEGF-R2 dual ... TU2218, a first-in-classoral dual inhibitor against TGFβRI and VEGFR2 was well-tolerated in the monotherapy and in the combination therapy with pembrolizumab.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05204862

NCT05204862 | Phase 1/2 Study of TU2218 Alone and in ... This study consists of Part A for monotherapy and Part B for combination therapy to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03019-3/fulltext

1043P First-in-human study of TU2218, TGFβRI and ... This is a first-in-human study to investigate the safety and tolerability of TU2218 mono- and combination therapy with pembrolizumab.

4. 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 ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02592-4/fulltext

1014P Phase Ib trial results of safety, pharmacokinetics ... TU2218, a first-in-class dual inhibitor against TGFβ-RI and VEGF-R2 was safe and well-tolerated in combination with pembrolizumab.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2691

Phase 2 trial of TU2218, TGFβ-RI, and VEGF-R2 dual ... In vitro and in vivo nonclinical studies have shown that TU2218 reduced the growth and migration/invasion of tumor cells and increased antitumor ...