MC# 22-04 - A Phase I Study of BAL0891 as Monotherapy and in Combination with Chemotherapy in Patients with Advanced Solid Tumors
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Agent(s): BAL0891
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Disease Type(s): Solid Tumor
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Phase(s): I
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Drug Classification(s): Small Molecule, Targeted Therapy
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Molecular Target(s): PLK, TTK
Mechanism of Action
BAL0891 is a small-molecule, first-in-class mitotic checkpoint inhibitor. The dual action of BAL0891, with prolonged TTK and transient PLK1 inhibition, may lead to a rapid disruption of the spindle assembly checkpoint (SAC) driving the cells through mitosis before the chromosomes are properly aligned leading to premature tumor cell division and tumor cell death.
Purpose
In this study, the sponsor and investigators want to learn:
- How much of BAL0891 can be given with an acceptable level of side effects alone or in combination
- The effects of BAL0891 (good and bad)
- How much of BAL0891 is absorbed into the blood and how fast it is removed
Inclusion Criteria
- 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.
- 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.
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
- For patients enrolled from Dose Level (DL) 1.4 of Substudy 1 onwards and for all patients in Substudies 2 and 3, measurable tumor disease per Response Evaluation Criteria in Solid Tumors 1.1 criteria (RECIST 1.1), i.e., a minimum of one target lesion.
- Adequate organ functions as indicated by the following Screening visit local laboratory values (i.e. clinical chemistry, hematology, and urinalysis) to be within clinically acceptable ranges at the Screening visit.
- For women of child-bearing potential, negative serum human chorionic gonadotropin (hCG)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 90 days after the last dose of either investigational drug, and
- comply with the contraception requirements
Exclusion Criteria
- 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.
- 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.
- Any unresolved (at the time of Screening visit) clinically significant Grade ≥ 2 toxicity (except for Grade 2 alopecia, and Grade 2 platinum-therapy-related neuropathy from previous anti-tumor treatment).
- History of clinically significant cardiac disorders
- Grade 3 adipositas, i.e., BMI ≥ 40 kg/m2
- Requiring supportive care treatment with hematopoietic growth factors within the 2 weeks prior to treatment allocation.
- 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.
- 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, or hepatic, renal, respiratory, or psychiatric illness.
- 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.
- Pregnant or breastfeeding.
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
