BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia

NCT05768932 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TTK-CS-101
• Study Type: interventional
• Target: 260
• Locations: 2 countries
• Sites: 15

Brief Summary

This study is a multiple cohort, multicenter, open-label Phase 1 study with dose-escalation substudies investigating intravenous (IV) BAL0891 as monotherapy, and in combination with tislelizumab or paclitaxel, to determine the safety and tolerability of increasing doses of BAL0891 in patients with advanced solid tumors or relapsed or refractory acute myeloid leukemia. An adaptive model-based design will be used to guide the dose escalation. Subject assignment to Substudy 1, 2, 3 and 4 will be finalized following approval from the investigator and sponsor. The dose-expansion stage will be conducted with the RP2D to further evaluate the preliminary anti-tumor activity, safety, and tolerability in metastatic TNBC and GC.

Conditions

Advanced Solid Tumor; TNBC - Triple-Negative Breast Cancer; Gastric Cancer; Leukemia Acute Myeloid Leukemia (AML)

Keywords

carcinoma; paclitaxel; BAL0891; tislelizumab

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Safety is collected through summaries of AE(Adverse Event)s, safety laboratory evaluations, PK evaluations, physical examinations, vital signs, and ECGs using CTCAE v5.0.

  After first dose, up to 2 years

• Part 1: Number of Participants With the DLT (Dose-limiting toxicity)s as a Measure of maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)

  DLTs are collected through BLRM-EWOC.

  After first dose and within 7 days of End of Treatment, up to 2 years

• Part 2: Overall response rate (ORR) for all subjects

  The proportion of patients with confirmed complete response (CR) or partial response (PR) by RECIST 1.1/iRECIST (substudy 2 only) during the dose expansion phase.

  Every 3 months (±14 days) after first dose, up to 2 years

Secondary Outcomes (17)

• Part 1: Pharmacokinetics (PK) parameters for all subjects

  Within 7 days of End of Treatment, up to 2 years

• Part 1: Absolute neutrophil count (ANC) for all subjects

  Within 7 days of End of Treatment, up to 2 years

• Part 1, 2: Overall response rate (ORR) for all subjects

  Every 3 months (±14 days) after first dose, up to 2 years

• Part 1, 2: Disease control rate (DCR) for all subjects

  Within 7 days of End of Treatment, up to 2 years

• Part 1, 2: Progression-free survival (PFS) for all subjects

  Within 7 days of End of Treatment, up to 2 years

Study Arms (8)

Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy

EXPERIMENTAL

Increasing doses of BAL0891 will be administered IV on D1 and D8 Q3W (Regimen A). BAL0891 will be investigated in a dose range of 5-480 mg with Regimen A. Optionally, and based on cumulative safety, PK, and PD data, BAL0891 may be administered on D1 Q3W (Regimen B), D1 and D15 Q4W (Regimen C), or on D1, D8, and D15 Q4W (Regimen D).

Drug: BAL0891

Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with tislelizumab

EXPERIMENTAL

Increasing doses of BAL0891 will be administrated IV on D1 and D15 with tislelizumab administration on D8 Q3W. The starting dose of BAL0891 for combination will be at approximately 50% of the BAL0891 monotherapy MTD determined in Substudy 1 and tislelizumab dose will be 200mg IV.

Drug: BAL0891; Combination Product: Tislelizumab

Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel

EXPERIMENTAL

Paclitaxel will be dosed at 70 mg/m2 on D1, D8, and D15 Q4W, with an option to use 80 mg/m2 (either instead of, or after exploring, 70 mg/m2) if the cumulative data collected at that time support a higher dose of paclitaxel.

Drug: BAL0891; Combination Product: Paclitaxel

Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy)

EXPERIMENTAL

BAL0891 will be administered intravenously on D1 and D8, Q3W for cohorts 1. The investigation will focus on the RP2D determined during the dose escalation phase of the study. Specifically, cohorts 1 will utilize the RP2D established in substudy 1 of the dose escalation phase.

Drug: BAL0891

Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy)

EXPERIMENTAL

BAL0891 will be administered intravenously on D1 and D8, Q3W for cohorts 2. The investigation will focus on the RP2D determined during the dose escalation phase of the study. Specifically, cohorts 2 will utilize the RP2D established in substudy 1 of the dose escalation phase.

Drug: BAL0891

Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel)

EXPERIMENTAL

BAL0891 will be administered intravenously on D1 and D15, Q4W for cohorts 3 . The investigation will focus on the RP2D determined during the dose escalation phase of the study. Specifically, cohorts 3 will utilize the RP2D established in substudy 3 of the dose escalation phase.

Drug: BAL0891; Combination Product: Paclitaxel

Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel)

EXPERIMENTAL

BAL0891 will be administered intravenously on D1 and D15, Q4W for cohorts 4. The investigation will focus on the RP2D determined during the dose escalation phase of the study. Specifically, cohorts 4 will utilize the RP2D established in substudy 3 of the dose escalation phase.

Drug: BAL0891; Combination Product: Paclitaxel

Part 1: Substudy 4, Dose-escalation substudy of BAL0891 monotherapy in r/r AML

EXPERIMENTAL

BAL0891 will be administered intravenously on Day 1 and Day 8 every three weeks (Regimen A). Dose exploration will proceed until the highest planned dose level (DL) is determined to be safe and tolerable, or the MTD/RP2D is identified.

Drug: BAL0891

Interventions

BAL0891 DRUG

BAL0891 is a dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1)

Also known as: TTK-CS-101

Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy; Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with tislelizumab; Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel; Part 1: Substudy 4, Dose-escalation substudy of BAL0891 monotherapy in r/r AML; Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy); Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy); Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel); Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel)

Tislelizumab COMBINATION_PRODUCT

Tislelizumab a humanized IgG4 anti-PD-1 monoclonal antibody

Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with tislelizumab

Paclitaxel COMBINATION_PRODUCT

Paclitaxel is a natural product with antitumor activity

Also known as: Taxol

Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel; Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel); Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel)

Eligibility Criteria

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

You may qualify if:

• Informed consent signed by the patient prior to any study-related procedure indicating that they understand the purpose of, and procedures required for, the study, and are willing to participate in the study.
• Male or female aged ≥18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
• Patients with incurable advanced/metastatic solid tumor disease refractory to or intolerant of existing therapy known to provide clinical benefit for their condition.
• Note: Patients with non-CNS tumors participating during dose escalation may have inactive CNS metastasis, defined as 4 weeks after either brain metastasis resection or radiation, and a) all residual neurological symptoms resolved to grade ≤ 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up imaging shows no new lesions appearing.
• Patients enrolled in Dose Expansion only
• TNBC cohorts i. Must have histologically confirmed breast adenocarcinoma that is unresectable, loco-regional, or metastatic.
• ii. Must have source data documented pathologically confirmed triple negative breast cancer, defined as both of the following.
• Estrogen receptor (ER) and progesterone receptor (PgR) negative: \<1% of tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER or PgR (positive intrinsic controls)
• Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines
• IHC 0 or 1 fluorescence in situ hybridization (FISH) negative (or equivalent negative test)
• Patients with IHC 2 must have a negative by FISH (or equivalent negative test) iii. Patients with a history of different breast cancer phenotypes (i.e., ER/PgR/HER2 Positive) must obtain pathological confirmation of triple-negative disease in at least one of the current sites of metastasis.
• iv. Must have progression on or after therapy containing anthracycline and/or a taxane. Subjects must have received anthracycline and/or a taxane based regimen or other chemotherapy / targeted therapy regimen if anthracycline or taxane was contraindicated or another available approved targeted agent was contraindicated. At time of enrolment, patients must have progressed on, be intolerant of, or be ineligible for, all available standard of care therapies with proven benefit.
• GC cohort i. Must have a histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
• ii. Must have progression on or after therapy containing platinum/fluoropyrimidine. Subjects must have received platinum-based chemotherapy or other chemotherapy regimen if platinum-based chemotherapy was contraindicated or another available approved targeted agent unless the targeted agent was contraindicated. At time of enrolment, patients must have progressed on, be intolerant of, or be ineligible for, all available standard of care therapies with proven benefit.
• iii. Documentation of HER2/neu status. Patients who are HER2/neu-positive must be treated with a HER2/neu inhibitor, and subjects should have progressed on or be intolerant to the targeted therapy or subjects must have received other chemotherapy regimen if HER2/neu inhibitor was contraindicated or another available approved targeted agent unless the targeted agent was contraindicated. At time of enrolment, patients must have progressed on, be intolerant of, or be ineligible for, all available standard of care therapies with proven benefit.

Sponsors & Collaborators

• SillaJen, Inc.: lead

Study Sites (15)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

RECRUITING

University of Miami Health System

Coral Gables, Florida, 33146, United States

RECRUITING

Winship Cancer Institute / Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Weill Cornell Medicine- NewYork-Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

ACTIVE NOT RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

WITHDRAWN

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Korean University Anam Hospital

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Stomach Neoplasms; Leukemia, Myeloid, Acute; Carcinoma

Interventions

tislelizumab; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• SillaJen Inc.

  SillaJen, Inc.

  STUDY DIRECTOR

Central Study Contacts

SillaJen Inc.

CONTACT

02-368-2600; patient_inquiry@sillajen.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: January 29, 2023
• First Posted: March 15, 2023
• Study Start: December 14, 2022
• Primary Completion (Estimated): December 24, 2026
• Study Completion (Estimated): December 24, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); KR (6)