Trial Title:
BAL0891 in Patients With Advanced Solid Tumors
NCT ID:
NCT05768932
Condition:
Advanced Solid Tumor
TNBC - Triple-Negative Breast Cancer
Gastric Cancer
Conditions: Official terms:
Triple Negative Breast Neoplasms
Paclitaxel
Carboplatin
Conditions: Keywords:
carcinoma
carboplatin
paclitaxel
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BAL0891
Description:
BAL0891 is a dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1
(PLK1)
Arm group label:
Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy
Arm group label:
Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin
Arm group label:
Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel
Arm group label:
Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy)
Arm group label:
Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy)
Arm group label:
Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel)
Arm group label:
Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel)
Other name:
TTK-CS-101
Intervention type:
Combination Product
Intervention name:
Carboplatin
Description:
Carboplatin is an Antineoplastic agent
Arm group label:
Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with carboplatin
Intervention type:
Combination Product
Intervention name:
Paclitaxel
Description:
Paclitaxel is a natural product with antitumor activity
Arm group label:
Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel
Arm group label:
Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel)
Arm group label:
Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel)
Other name:
Taxol
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. An adaptive
model-based design will be used to guide the dose escalation. Subject assignment to
Substudy 1, 2 and 3 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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Male or female aged ≥18 years (or ≥ 19 years according to local regulatory
guidelines) at the time of screening.
3. 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.
4. 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 documented pathologically confirmerd triple negative breast
cancer, defined as both of the following.
1. Estrogen receptor (ER) and progresterone 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)
2. Human epidermal growth factor receptor 2 (HER2) negative as per American
Society of Clincal 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.
- 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 or
refused standard therapy.
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 refused standard therapy.
iv.Subjects may have received no more than 3 lines of prior therapy for the advanced
disease (if a subject progressed within 6 months of completing adjuvant therapy,
this would count as a prior line of therapy).
5. Patients enrolled in Dose Expansion only, patient must have undergone a minimum of 1
prior systemic regimen for advanced or metastatic disease.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
7. For patients enrolled from DL1.4 of Substudy 1 onwards and for all patients in
Substudies 2 and 3 and all four dose expansion cohorts, measurable tumor disease per
Response Evaluation Criteria in Solid Tumors 1.1 criteria (RECIST 1.1), i.e., a
minimum of one target lesion.
8. Adequate organ functions as indicated by the following Screening visit local
laboratory values:
- Hemoglobin ≥ 9 g/dL (criterion must be met without erythropoietin dependency
and without packed red blood cell transfusion within the last 4 weeks)
- ANC ≥ 2.0 × 109/L; criterion must be met without growth factor (e.g., G-CSF, GM
CSF, etc.) administration within the last 2 weeks
- Platelets ≥ 100 × 109/L
- Total bilirubin ≤ 1.5 × ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) baseline
levels ≤ 1.5 × ULN, with the option for AST/ALT ≤ 3.0 × ULN, or ≤ 5.0 × ULN for
patients with liver metastasis, upon accumulating evidence for absence of liver
toxicity in biologically active DLs
- Albumin ≥ 2.8 g/dL
- CLCR ≥ 60 mL/min (as calculated by the Cockcroft-Gault formula)
- For women of child-bearing potential, negative serum human chorionic
gonadotropin (hCG)
9. Men/women of child-producing/bearing potential must agree to:
- avoid impregnating a partner or becoming pregnant, respectively, during the
study, and for at least 6 months after the last dose of either investigational
drug, and
- comply with the contraception requirements set out.
Exclusion Criteria:
1. Receipt of treatment before the first dose of study drug (Cycle 1 D1) within an
interval shorter than the following, as applicable:
- One chemotherapy or biological (e.g., antibody, antibody drug-conjugate) cycle
interval
- 5 half-lives or 28 days whichever is shorter of any small molecule
investigational or licensed medicinal product
- 2 weeks, for any investigational medicinal product (IMP) with an unknown
half-life
- 4 weeks of curative radiotherapy
- 7 days of palliative radiotherapy.
2. Either receipt of ≥ 4 prior lines of cytotoxic chemotherapy-containing, anti-cancer
treatment (both in the [neo]adjuvant and advanced/metastatic setting), or episode(s)
of neutropenic sepsis or prolonged antibiotic treatment (> 2 weeks treatment and/or
hospitalization for either Grade 4 neutropenia, Grade ≥ 3 neutropenia-associated
infection or neutropenic fever) during either of the last two anti-cancer
treatments. (dose escalation and dose expansion phases of the study)
3. Prior radiation of > 25% of hematopoietic bone marrow volume in long bones, pelvis,
and lumbar spine (per Investigator assessment) and/or prior bone marrow/stem cell
transplantation.
4. Any unresolved (at the time of Screening visit) clinically significant Grade ≥ 2
toxicity (except for Grade 2 alopecia, stable Grade 2 endocrine disorders and Grade
2 platinum-therapy related neuropathy from previous anti-tumor treatment).
5. History of clinically significant cardiac disorders:
- New York Heart Association Class II to IV congestive heart failure, within 6
months of the first dose of study drug
- Any arterial thrombotic event, including myocardial infarction, unstable
angina, cerebrovascular accident, or transient ischemic attack, within 6 months
of the first dose of study drug
- Concurrent and clinically significant abnormalities on ECG at Screening,
including a QTcF > 450 ms for males or > 460 ms for females (mean values from
triplicate ECGs).
6. Lack of recovery from major (e.g., open abdominal) surgery after 4 weeks, or major
elective surgery is planned during the foreseeable duration of the study.
7. Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV;
known HIV 1/2 antibodies positive).
8. Active hepatitis C, active hepatitis B, or chronic hepatitis B with an HBV DNA ≥ 100
IU/mL without current antiviral therapy.
Note: The initial serology testing during the Screening visit for evaluating an
active or chronic Hepatitis B infection has to include the following markers: HBsAg,
HBcAb and HBsAb. In the event of a positive HBsAg test result, the patient cannot be
enrolled. In the event of a positive HBcAb and negative HBsAb test result, an HBV
DNA RT-PCR test has to be performed, and the patient can be only enrolled if HBV DNA
< 100 IU/mL and the patient receives adequate antiviral therapy.
Note: The serology testing during the Screening visit for evaluating an active or
chronic Hepatitis C infection includes Hepatitis C antibody (HepCAb), followed by
Hepatitis C virus RNA by PCR if HepCAb is positive. Patients who test HepCA positive
but have an HCV RNA negative test result due to prior treatment or natural
resolution may be enrolled.
9. Severe bacterial, fungal, viral, and/or parasitic infections treated with
therapeutic oral or IV medication at the time of first dose of study drug
administration.
10. Grade 4 Obesity,.i.e., BMI ≥ 40 kg/m2
11. For Substudy 2, receipt of prior BAL0891 or contraindicated to receive carboplatin
(e.g., history of severe allergic reactions to cisplatin or other
platinum-containing compounds, severe bone marrow suppression [baseline ANC < 2.0 ×
109/L], or significant bleeding).
12. For Substudy 3 and cohorts 3 and 4 of the dose expansion phase, receipt of prior
BAL0891 or contraindicated to receive paclitaxel (e.g., history of prior severe
hypersensitivity reactions to paclitaxel, severe bone marrow suppression [baseline
ANC < 2.0 × 109/L]), and/or receipt of mandatory premedications (e.g., H2
antagonists or alternatives, and corticosteroids, diphenhydramine, or alternatives).
13. Known hypersensitivity or allergy to any component of the formulations of BAL0891
(e.g., cyclodextrins), carboplatin (for Substudy 2 only), or paclitaxel (for
Substudy 3 and cohorts 3 and 4 of dose expansion phase).
14. Requiring supportive care treatment with hematopoietic growth factors within the 2
weeks prior to treatment allocation.
Note: Biologic response modifiers administered for erythropoiesis (e.g.,
erythropoietin, darbepoetin alpha) may be administered to patients who experienced
severe bone marrow suppression during study treatment. Granulocyte growth factors
(e.g., G-CSF, GM-CSF, etc.) will be administered according to the Investigator's
standard practice or American Society of Clinical Oncology (ASCO) guidelines (Smith
2015).
15. Treatment with systemic corticosteroids (except for steroidal replacement therapy
with 10 mg or less of prednisone or equivalent) or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within 2 weeks prior to first dose of study drug, or anticipated
requirement for systemic immunosuppressive medications during the study.
Note: Inhaled, intranasal, intraocular, topical corticosteroids, and intra articular
joint injections of corticosteroids are allowed.
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
17. Any other uncontrolled intercurrent illness that would unduly increase the risk of
toxicity or limit compliance with study requirements, including but not limited to
ongoing or active symptomatic infection, uncontrolled diabetes mellitus,
uncontrolled hypertension (systolic blood pressure >160 mmHg; diastolic blood
pressure >100 mmHg), or hepatic, renal, respiratory, or psychiatric illness.
18. A history or evidence of psychiatric disorder, substance abuse, or any other
clinically significant disorder, condition, or disease that, in the opinion of the
Investigator or the Sponsor would pose a risk to the safety of the patient, or would
interfere with the study evaluation, procedures, or completion.
19. Pregnant or breastfeeding.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami Health System
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
University of Miami Health System
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10461
Country:
United States
Status:
Recruiting
Contact:
Last name:
Montefiore Medical Center
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
OHSU Knight Cancer Institute
Facility:
Name:
Mary Crowley Cancer Research
Address:
City:
Dallas
Zip:
75230
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mary Crowley Cancer Research
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Asan Medical Center
Facility:
Name:
Korean University Anam Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Korean University Anam Hospital
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Samsung Medical Center
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Seoul National University Hospital
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Severance Hospital, Yonsei University Health System
Start date:
December 14, 2022
Completion date:
March 24, 2026
Lead sponsor:
Agency:
SillaJen, Inc.
Agency class:
Industry
Source:
SillaJen, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05768932
