What side effects are associated with this type of intervention?

Common treatments for solid tumors, including chemotherapeutic agents like paclitaxel, cisplatin, and carboplatin, as well as targeted therapies such as checkpoint inhibitors, often result in a range of side effects. Hematologic toxicities such as neutropenia, anemia, and thrombocytopenia are frequent, leading to increased infection risk and fatigue. Gastrointestinal disturbances, including nausea, vomiting, and diarrhea, are also common. Other systemic effects can include fatigue, neuropathy, and, in the case of checkpoint inhibitors, immune-related adverse events like pneumonitis, rash, and pruritus. These side effects necessitate careful monitoring and supportive care during treatment.

What prior FDA approvals exist?

Several drugs have received FDA approval for the treatment of advanced solid tumors, particularly those with mechanisms similar to the antitumor agent TU2218. Notable examples include immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways to enhance the immune system's ability to fight cancer. Additionally, targeted therapies like bevacizumab, which inhibits angiogenesis, and various tyrosine kinase inhibitors have been approved for specific solid tumors. These treatments have demonstrated significant efficacy in improving survival and response rates in patients with advanced solid tumors.

What other types of research exist?

Promising novel alternatives to TU2218 for solid tumor patients include STK899704, which has shown comparable efficacy to 5-fluorouracil, and PTX-loaded 4-arm-PEG(5K)-TPGS nanoparticles, which demonstrated greater cytotoxicity and improved tumor growth inhibition compared to Taxol® in preclinical models.

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Virus Therapy

TU2218 + Checkpoint Inhibitors for Solid Tumors

Phase 1 & 2

Recruiting

Research Sponsored by TiumBio Co., Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A washout period of 4 weeks for any biologic material and a minimum of 5 half-lives for any chemotherapy is required prior to the start of treatment with resolution of any toxicity to maximum Grade 1 (except alopecia)

Adequate hepatic and renal functions defined by: Total bilirubin ≤1.5 × ULN, AST and ALT ≤3 × ULN; if liver metastases are present, then ≤5 × ULN is allowed, Estimated creatinine clearance >60 mL/min according to the Cockcroft-Gault formula

Must not have

Regular use of aspirin (>325mg/day) or other non-steroidal anti-inflammatory drugs with antiplatelet activity or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol within 10 days of first administration of study treatment

Myocardial infarction within 6 months prior to screening, or pericardial effusion

Timeline

Screening 3 weeks

Treatment Varies

Follow Up date of first study treatment to death from any cause (up to 24 months)

Awards & highlights

Summary

This trial tests a new drug, TU2218, to see if it can safely help treat patients with advanced solid tumors by reducing tumor size. Sunitinib malate has shown promising clinical activity in the treatment of advanced solid tumors.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical reactions seen with cancer therapies such as immune-related inflammation in various organs due to checkpoint inhibitors like Anti-PD-1 antibodies. Other common side effects could involve fatigue, digestive disturbances, skin reactions, blood count changes leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My liver and kidney functions meet the required levels.

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I finished radiotherapy at least 2 weeks ago with minimal side effects.

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I am a woman who can have children and have a recent negative pregnancy test.

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My advanced cancer has not responded to standard treatments, including anti-PD-(L)1 therapy.

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My blood counts and clotting factors are within a healthy range.

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I am fully active or can carry out light work.

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I can swallow pills.

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My advanced cancer has no effective standard treatment or treatments have failed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have not had a heart attack or fluid around my heart in the last 6 months.

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I cannot stop taking my chronic steroids or other immune-suppressing drugs.

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I have a moderate or severe heart valve problem.

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I cannot or will not stop taking certain strong medications at least 8 days before the study starts.

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I am not pregnant or at risk of becoming pregnant and agree to use effective birth control or practice abstinence.

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I haven't had heart attacks, strokes, blood clots in my lungs or legs, or blocked arteries in the last year.

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I am currently on antibiotics for an infection.

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I cannot stop my blood thinning medication for the duration of the study and 28 days after.

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I have severe heart failure.

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My heart tests show high troponin or BNP levels.

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I am not willing to stop taking herbal supplements or traditional medicines.

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I have or had lung inflammation not caused by an infection.

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I have been treated before for my condition with drugs targeting TGF-β.

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I have a history of aneurysm in my heart or major blood vessels.

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I have not had major surgery in the last 28 days and do not plan any during the study.

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I am currently breastfeeding.

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I am not currently using any non-permitted drugs or substances.

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I cannot or will not stop taking stomach acid-reducing drugs for 8 days before the study starts.

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I have previously taken anti-PD(L)1 drugs without severe side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ date of first study treatment to death from any cause (up to 24 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~date of first study treatment to death from any cause (up to 24 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and date of first study treatment to death from any cause (up to 24 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Maximum Tolerated Dose (MTD) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)

Phase 2: Overall Response rate (ORR) of TU2218 administered alone (Part A) and in combination with anti-PD-1 antibody (Part B)

Secondary study objectives

Area under the plasma concentration versus time curve (AUC) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody

Clearance (CL) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody

Clinical benefit rate (CBR)

+6 more

Side effects data

From 2021 Phase 2 trial • 22 Patients • NCT03019640

100%

Anemia

100%

Neutrophil count decreased

100%

White blood cell decreased

100%

Nausea

100%

Fever

100%

Lymphocyte count decreased

100%

Platelet count decreased

95%

Diarrhea

82%

Hyperglycemia

77%

Mucositis oral

77%

Fatigue

64%

Sinus tachycardia

59%

Anorexia

59%

Hypotension

55%

Rash maculo-papular

55%

Constipation

55%

Edema limbs

55%

Hypophosphatemia

50%

Headache

45%

Alanine aminotransferase increased

45%

Hypoalbuminemia

45%

Hypocalcemia

41%

Hypokalemia

41%

Dizziness

36%

Anxiety

36%

Hyponatremia

32%

Vomiting

32%

Hypertension

32%

Cough

32%

Chills

32%

Insomnia

32%

Investigations

32%

Febrile neutropenia

27%

Aspartate aminotransferase increased

27%

Alkaline phosphatase increased

27%

Pain

23%

Arthralgia

23%

Hiccups

23%

Dysphagia

23%

Esophagitis

23%

Hypomagnesemia

23%

Infections and infestations

18%

Hemorrhoids

18%

Allergic rhinitis

18%

Abdominal pain

18%

Dehydration

18%

Dyspnea

18%

Generalized muscle weakness

18%

Hypoxia

14%

Bloating

14%

Hypermagnesemia

14%

Dyspepsia

14%

Paresthesia

14%

Rectal pain

14%

Infusion related reaction

14%

Immune system disorders

14%

INR increased

14%

Pleural effusion

Arthritis

Blood bilirubin increased

Back pain

Upper respiratory infection

Cholesterol high

Bone pain

Creatinine increased

Sore throat

Dry skin

Dysgeusia

Hypernatremia

Renal and urinary disorders

Skin ulceration

Flushing

Non-cardiac chest pain

General disorders and administration site conditions

Hyperuricemia

Nasal congestion

Papulopustular rash

Hypercalcemia

Atrial fibrillation

Bladder infection

Gastrointestinal pain

Ear pain

Eye disorders

Flatulence

Nervous system disorders

Rash acneiform

Skin hyperpigmentation

Tremor

Encephalopathy

Urinary frequency

Respiratory failure

Lung

Epistaxis

Acute kidney injury

Atelectasis

Weight gain

Gastroesophageal reflux disease

Urinary tract infection

Thromboembolic event

Edema face

Endocrine disorders

Metabolism and nutrition disorders

Mucosal infection

Neck pain

Prostatic obstruction

Pulmonary edema

Hematuria

Hemorrhoidal hemorrhage

Hypoglycemia

Musculoskeletal and connective tissue disorder

Myalgia

Hypothyroidism

Lung infection

Lymph node pain

Lymphocyte count increased

Pain in extremity

Peripheral motor neuropathy

Restlessness

Sinus bradycardia

Sinusitis

Skin and subcutaneous tissue disorder

Urinary tract pain

Vascular disorders

Ileus

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Chemotherapy, NK Infusion, Stem Cell Transplant)

Trial Design

5Treatment groups

Experimental Treatment

Group I: TU2218 Phase 2aExperimental Treatment1 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 1aExperimental Treatment1 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 EffectExperimental Treatment1 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 2bExperimental Treatment2 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 1bExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Anti-PD-1 antibody

2018

Completed Phase 2

~40

0 / 29Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors often include antitumor agents such as checkpoint inhibitors and targeted therapies. Checkpoint inhibitors, like anti-PD-1 and anti-CTLA-4 antibodies, work by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. Targeted therapies, on the other hand, focus on specific molecular targets associated with cancer growth and progression, such as tyrosine kinase inhibitors that block signals needed for tumors to grow. These treatments are crucial for solid tumor patients as they offer more personalized and potentially effective options with fewer side effects compared to traditional chemotherapy.

Current trends and future directions in the genetic therapy of human neoplastic disease.