Phase 1/2 Study of TU2218 Alone and in Combination With Checkpoint Inhibitors in Patients With Advanced Solid Tumors

NCT05204862 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TUC1PI-01
• Study Type: interventional
• Target: 240
• Locations: 2 countries
• Sites: 3

Brief Summary

This study consists of Part A for monotherapy and Part B for combination therapy to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy of TU2218 in patients with advanced solid tumors. The main purpose of Phase 1 is to determined the recommended Phase 2 dose (RP2D) of TU2218 and the main purpose of Phase 2 is to evaluate the antitumor activity of TU2218 at RP2D.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

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

  The MTD is determined as DLTs.

  From the beginning of Cycle 1 through Cycle 2 (each cycle is 21 days)

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

  ORR is defined as the proportion of patients who have a PR and CR.

  24 weeks

Secondary Outcomes (9)

• Incidence of treatment-emergent AEs

  approximately 13 months

• Peak Plasma Concentration (Cmax) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody

  Cycle 1

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

  Cycle 1

• Terminal half-life (t1/2) of TU2218 for TU2218 alone and in combination with anti-PD1 antibody

  Cycle 1

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

  Cycle 1

Study Arms (5)

TU2218 Phase 1a

EXPERIMENTAL

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

Drug: TU2218

TU2218 Food Effect

EXPERIMENTAL

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

Drug: TU2218

TU2218 + Anti-PD-1 antibody Phase 1b

EXPERIMENTAL

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

Drug: TU2218; Drug: Anti-PD-1 antibody

TU2218 Phase 2a

EXPERIMENTAL

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

Drug: TU2218

TU2218 + Anti-PD-1 antibody Phase 2b

EXPERIMENTAL

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

Drug: TU2218; Drug: Anti-PD-1 antibody

Interventions

TU2218 DRUG

orally administered

TU2218 + Anti-PD-1 antibody Phase 1b; TU2218 + Anti-PD-1 antibody Phase 2b; TU2218 Food Effect; TU2218 Phase 1a; TU2218 Phase 2a

Anti-PD-1 antibody DRUG

Intravenously administered

TU2218 + Anti-PD-1 antibody Phase 1b; TU2218 + Anti-PD-1 antibody Phase 2b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females at least 18 years of age at the time of consent (ie, screening), or according to local regulatory requirement if the legal age for consenting for study participation is more than 18 years.
• Life expectancy ≥12 weeks as judged by the Investigator.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; except for Phase1a that can enroll patients with either measurable and/or non-measurable disease.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Able to swallow capsules.
• Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, or standard therapy has failed (Phase 1a).
• Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, and for which standard therapy containing an anti-PD-(L)1 agent has failed after an initial response or stabilization of at least 4-month duration (Phase 1b and 2a).
• Adequate hematological function, coagulation defined by:
• Absolute neutrophil count ≥1,500 cells/μL
• Platelet count ≥100,000/μL
• Hemoglobin ≥9.0 g/dL
• International normalized ratio \<1.5 × the upper limit of normal (ULN)
• 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

You may not qualify if:

• Myocardial infarction within 6 months prior to screening, or pericardial effusion.
• History of cardiac or aortic surgery within 6 months prior to screening.
• Unstable angina pectoris, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis; arterial occlusive disease in the past 12 months.
• Congestive heart failure of New York Heart Association class III/IV.
• Major arrhythmia or abnormalities identified by ECG per Investigator's judgment.
• Uncontrolled hypertension (as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) during the screening period.
• Elevated troponin 1 levels (Grade 3) at screening or known to have persistently elevated brain natriuretic peptide.
• Active and clinically significant bacterial, fungal, or viral infection, including active or known history of hepatitis B virus (defined as hepatitis B surface antigen \[HbsAg\] reactive), or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid \[qualitative\] is detected), known human immunodeficiency virus or acquired immunodeficiency syndrome related illness. However, an inactive hepatitis B virus carrier can be enrolled
• Current or history of interstitial pneumonitis.
• Uncontrolled metastatic disease to the brain or central nervous system, massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement that is at the discretion of the Investigator. Note: Pleural effusion should be defined by Investigator's discretion.
• Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
• Received prior treatment targeting the signaling pathway of TGF-β.
• Tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed.
• History of severe bleeding. Unable to stop anticoagulation therapy with heparin, low molecular weight heparin, vitamin K antagonists, antiplatelet agents, or factor Xa inhibitors throughout the study and for at least 28 days after the last administration of study treatment.
• 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.

Sponsors & Collaborators

• TiumBio Co., Ltd.: lead

Study Sites (3)

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

MeSH Terms

Interventions

spartalizumab

Study Officials

• TU2218

  TiumBio Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

82-31-600-1500; nce401_tu2218@tiumbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 24, 2022
• Study Start: December 2, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); KR (2)