BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia
- Conditions
- Advanced Solid TumorTNBC - Triple-Negative Breast CancerGastric CancerLeukemia Acute Myeloid Leukemia (AML)
- Interventions
- Drug: BAL0891Combination Product: PaclitaxelCombination Product: Carboplatin
- Registration Number
- NCT05768932
- Lead Sponsor
- SillaJen, Inc.
- 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 carboplatin 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.
- Detailed Description
Substudy 1 (monotherapy dose-escalation cohorts) This study will be initiated with enrollment into Substudy 1 and will estimate the safety, tolerability, PK, and PD of increasing doses of BAL0891 in patients with advanced solid tumors. The starting dose will be 5 mg based on the GLP (Good Laboratory Practice) toxicology studies. Dose escalation will comprise a dose range from a dose of 5 mg up to a maximum absolute dose of 480 mg, with eight nominal dose levels (DLs) of 5 / 10 / 20 / 40 / 80 / 160 / 320 / 480 mg. Intra-patient dose escalations are only allowed for patients enrolled in single-patient DL Cohorts 1.1, 1.2, and 1.3. From DL Cohort 1.4 onwards, the projected maximum dose-escalation factor will be two-fold; if the DL cohort investigates an increased dose, dosing of the patients within the cohort must be separated by at least 7 days. For cohorts in which doses are not increased (including backfill enrollment), patients may be enrolled concurrently.
BAL0891 will be administered intravenously (IV) on Day (D) 1 and D8 every 3 weeks (Q3W); for the schedule of assessments of Regimen A. Alternative 21-day or 28-day dosing regimens may be investigated; for the schedule of assessments of Regimens B-D.
Substudies 2 and 3 (dose-escalation cohorts for combination regimens) Enrollment into Substudies 2 and 3 may commence as early as first signs of expected target toxicity and/or efficacy with Regimen A (or an alternative monotherapy regimen) have been observed, or alternatively, once the MTD of BAL0891 monotherapy has been assessed. Patients enrolled into Substudies 2 and 3 will be treated with increasing doses of BAL0891 in combination with carboplatin and paclitaxel, respectively, and dose escalation of both BAL0891 and carboplatin/paclitaxel if required will use the same cumulative BLRM-EWOC model as Substudy 1. The starting dose of BAL0891 in combination with carboplatin or paclitaxel will be a safe DL determined in Substudy 1 but not higher than approximately half the MTD. Backfill enrollment of up to a total of 30 additional patients for both substudies (who may be enrolled concurrently) may be used to better estimate the RP2D for each combination if required.
Substudy 4 (dose escalation cohort for monotherapy in r/r AML)
Substudy 4 will evaluate BAL0891 monotherapy in patients with relapsed/refractory AML (r/r AML) using the same BLRM-EWOC model and study design described for Substudy 1. BAL0891 will be administered intravenously on Day 1 and Day 8 every three weeks (Regimen A; see Table 13 for schedule of assessments). Dose exploration will proceed until the highest planned dose level (DL) is determined to be safe and tolerable, or the MTD/RP2D is identified.
Each DL cohort will enroll three patients, with DLT observation required before advancing to the next DL. From DL2 onward, the projected maximum dose-escalation factor will be two-fold, with concurrent enrollment allowed for cohorts without dose increases. Backfill enrollment may be conducted to refine the RP2D and further characterize safety, efficacy and PD.
Part 2 : Dose expansion The commencement of the dose expansion stage will follow the determination of the RP2D achieved during the dose-escalation phase. This stage will consist of four cohorts, each comprising 24 patients who have previously undergone at least one systemic regimen for advanced or metastatic disease. Specifically, two cohorts will be allocated for TNBC, investigating BAL0891 both as a monotherapy and in combination with Paclitaxel. Additionally, two cohorts will be designated for GC, investigating the outcomes of BAL0891 as a monotherapy and in combination with Paclitaxel.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 260
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin BAL0891 Carboplatin will be dosed at AUC5 Q3W, with an option to use AUC6 (either instead of, or after exploring, AUC5) if the cumulative data collected at that time support a higher dose of carboplatin. Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel BAL0891 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. Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel Paclitaxel 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. Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy) BAL0891 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. Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel) BAL0891 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. Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel) Paclitaxel 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. Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy BAL0891 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). Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin Carboplatin Carboplatin will be dosed at AUC5 Q3W, with an option to use AUC6 (either instead of, or after exploring, AUC5) if the cumulative data collected at that time support a higher dose of carboplatin. Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel) BAL0891 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. Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy) BAL0891 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. Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel) Paclitaxel 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. Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin BAL0891 Carboplatin will be dosed at AUC5 Q3W, with an option to use AUC6 (either instead of, or after exploring, AUC5) if the cumulative data collected at that time support a higher dose of carboplatin. Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin Carboplatin Carboplatin will be dosed at AUC5 Q3W, with an option to use AUC6 (either instead of, or after exploring, AUC5) if the cumulative data collected at that time support a higher dose of carboplatin. Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel Paclitaxel 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. Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy) BAL0891 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. Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel) BAL0891 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. Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel) Paclitaxel 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. Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel) Paclitaxel 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. Part 1: Substudy 4, Dose-escalation substudy of BAL0891 monotherapy in r/r AML BAL0891 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. Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy BAL0891 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). Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel BAL0891 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. Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy) BAL0891 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. Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel) BAL0891 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.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability After first dose, up to 2 years 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.
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) After first dose and within 7 days of End of Treatment, up to 2 years DLTs are collected through BLRM-EWOC.
Part 2: Overall response rate (ORR) for all subjects Every 3 months (±14 days) after first dose, up to 2 years The proportion of patients with confirmed complete response (CR) or partial response (PR) by RECIST 1.1 during the dose expansion phase.
- Secondary Outcome Measures
Name Time Method Part 1: Pharmacokinetics (PK) parameters for all subjects Within 7 days of End of Treatment, up to 2 years The area under the plasma concentration-time curve (AUC) by PK Sampling
Part 1: Absolute neutrophil count (ANC) for all subjects Within 7 days of End of Treatment, up to 2 years Duration of neutropenia by PD Sampling
Part 1, 2: Overall response rate (ORR) for all subjects Every 3 months (±14 days) after first dose, up to 2 years The proportion of patients with confirmed complete response (CR) or partial response (PR) by RECIST 1.1
Part 1, 2: Disease control rate (DCR) for all subjects Within 7 days of End of Treatment, up to 2 years The proportion of patients with confirmed CR, PR or stable disease (SD) by RECIST 1.1
Part 1, 2: Progression-free survival (PFS) for all subjects Within 7 days of End of Treatment, up to 2 years Measured from patient enrollment to disease progression date
Part 1, 2: Overall survival (OS) for all subjects Within 7 days of End of Treatment, up to 2 years Measured from from patient enrollment to time of death
Part 2: Safety evaluations for all subjects After first dose, up to 2 years Safety evaluations is focusing on key clinical evlauations such treatment-emergent adverse events (TEAE) using CTCAE v5.0.
Part 1: Efficacy Endpoints CR + CRh Rate (Substudy 4) Up to 2 years Proportion of patients achieving Complete Remission (CR) or CR with partial hematologic recovery (CRh) per European LeukemiaNet (ELN) 2022 guidelines.
Part 1: Efficacy Endpoints Duration of Remission (DoR) (Substudy 4) Up to 2 years Time from first documented CR/CRh until relapse or death.
Part 1: Efficacy Endpoints Transfusion Independence (TI) (Substudy 4) Up to 2 years Proportion of patients achieving red blood cell (RBC) and platelet transfusion independence for ≥56 consecutive days.
Part 1: Efficacy Endpoints CR/CRh without Measurable Residual Disease (MRD) (Substudy 4) Up to 2 years Proportion of patients achieving CR/CRh and MRD negativity.
Part 1: Efficacy Endpoints Composite Complete Remission (CRc) Rate (Substudy 4) Up to 2 years Proportion of patients achieving CR, CRh, or CR with incomplete hematologic recovery (CRi).
Part 1: Efficacy Endpoints Overall Response Rate (ORR) (Substudy 4) Up to 2 years Proportion of patients achieving CR, CRh, CRi, or Partial Remission (PR).
Part 1: Efficacy Endpoints Overall Survival (OS) (Substudy 4) Up to 2 years Time from first dose of BAL0891 to death from any cause.
Part 1: Efficacy Endpoints Event-Free Survival (EFS) (Substudy 4) Up to 2 years Time from first dose of BAL0891 to disease progression, relapse, or death.
Part 1: Efficacy Endpoints Time to Response (TTR) (Substudy 4) Up to 2 years Time from first dose of BAL0891 to first documented response.
Part 1: QTcF Interval Analysis From first dose to 30 days post last dose Analysis of QTcF interval data collected during BAL0891 monotherapy and the relationship between BAL0891 exposure and QTcF interval prolongation.
Trial Locations
- Locations (12)
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University of Miami Health System
🇺🇸Coral Gables, Florida, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korean University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of