BAL0891 + Chemotherapy for Solid Tumors

Recruiting at 21 trial locations

Overseen By SillaJen Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SillaJen, Inc.

Disqualifiers: Acute promyelocytic leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test the safety and tolerability of a new treatment called BAL0891, a TTK/PLK1 inhibitor, either alone or with other medications, for patients with advanced solid tumors or relapsed/refractory acute myeloid leukemia. Researchers seek to determine the right dose and assess whether it can slow or stop cancer growth. Suitable candidates include those with advanced solid tumors unresponsive to existing treatments or patients with acute myeloid leukemia that has recurred or resisted treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, and participants will be among the first to receive it.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, hydroxyurea is allowed during screening and the initial treatment cycle for certain patients, but no other anti-leukemic treatments are allowed during this period.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BAL0891 has potential as a treatment for solid tumors in early studies. This drug targets specific proteins in cancer cells to halt their growth. Although still in the early stages of human testing, studies suggest it has strong anti-tumor effects.

For those considering trial participation, understanding safety is crucial. In similar treatments, researchers typically start with low doses and gradually increase them to find a safe level for patients. BAL0891 is being tested alone and with other drugs like paclitaxel and tislelizumab, which are already used in cancer treatment and have well-known safety records.

While exact safety data for BAL0891 is still being gathered, the trial is designed to carefully monitor for any side effects as doses increase. This ensures the treatment remains as safe as possible for participants. Doctors will closely monitor participants' health to quickly address any issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BAL0891 because it offers a novel approach for treating solid tumors. Unlike standard treatments that often target cancer cells indiscriminately, BAL0891 works by exploiting specific molecular pathways to target cancer cells more precisely, potentially reducing side effects. Its ability to be combined with existing treatments like paclitaxel and tislelizumab also means it could enhance the effects of these drugs, offering a more comprehensive treatment strategy. Additionally, BAL0891's administration in various regimens allows for flexible dosing, which could improve patient outcomes and quality of life.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that BAL0891 affects two key proteins involved in cell division, helping to stop cancer cell growth. In this trial, some participants will receive BAL0891 as monotherapy, which early studies found effective against tumors. Others will receive BAL0891 combined with paclitaxel, a chemotherapy drug, potentially enhancing its effect. Additionally, one study arm combines BAL0891 with tislelizumab, an immunotherapy drug, which could further boost its cancer-fighting ability. Although more research is needed, these combinations appear promising for treating solid tumors. ^{1 3 6 7 8}

Who Is on the Research Team?

SillaJen Inc.

Principal Investigator

SillaJen, Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that are resistant or intolerant to existing treatments may join this trial. They should be in good physical condition (ECOG PS 0 or 1), have normal bilirubin levels, and adequate organ function including blood counts and liver enzymes. Women must not be pregnant, and all participants must agree to use contraception during the study.

Inclusion Criteria

For women of child-bearing potential, negative serum human chorionic gonadotropin (hCG)

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

For patients enrolled from DL1.4 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

Exclusion Criteria

Receipt of treatment before the first dose of study drug within specified intervals

I haven't fully recovered from major surgery within the last 4 weeks.

I haven't taken steroids or immunosuppressants recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive increasing doses of BAL0891 as monotherapy or in combination with chemotherapy to determine safety and tolerability.

Varies by cohort, up to 2 years

Every 3 weeks for monotherapy, every 4 weeks for combination therapy

Dose Expansion

Further evaluation of the preliminary anti-tumor activity, safety, and tolerability at the recommended Phase 2 dose (RP2D) in specific cancer cohorts.

Up to 2 years

Every 3 months for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• BAL0891

Trial Overview

The trial is testing BAL0891 alone and alongside chemotherapy drugs carboplatin or paclitaxel. It's an open-label Phase 1 study where doses of BAL0891 will gradually increase to assess safety and tolerability in patients with various types of advanced solid tumors.

How Is the Trial Designed?

Group I: Part 2 : Dose expansion, cohorts 4 GC (BAL0891 + Paclitaxel) Experimental Treatment 2 Interventions

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.

Group II: Part 2 : Dose expansion, cohorts 3 TNBC (BAL0891 + Paclitaxel) Experimental Treatment 2 Interventions

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.

Group III: Part 2 : Dose expansion, cohorts 2 GC (BAL0891 monotherapy) Experimental Treatment 1 Intervention

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.

Group IV: Part 2 : Dose expansion, cohorts 1 TNBC (BAL0891 monotherapy) Experimental Treatment 1 Intervention

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.

Group V: Part 1: Substudy 4, Dose-escalation substudy of BAL0891 monotherapy in r/r AML Experimental Treatment 1 Intervention

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.

Group VI: Part 1: Substudy 3, Dose-escalation substudy of BAL0891 in combination with paclitaxel Experimental Treatment 2 Interventions

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.

Group VII: Part 1: Substudy 2, Dose-escalation substudy of BAL0891 in combination with tislelizumab Experimental Treatment 2 Interventions

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.

Group VIII: Part 1: Substudy 1, Dose-escalation substudy of BAL0891 monotherapy Experimental Treatment 1 Intervention

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).

BAL0891 is already approved in United States for the following indications:

Approved in United States as BAL0891 for:

• None - Investigational New Drug application approved for Phase 1 study in advanced solid tumors

Who Is Running the Clinical Trial?

SillaJen, Inc.

Lead Sponsor

Trials

3

Recruited

810+

Published Research Related to This Trial

Polo-like kinases (Plks), particularly Plk1, play crucial roles in regulating cell processes like DNA replication and mitosis, and are often overexpressed in various cancers, making them important targets for cancer therapy.

Several Plk inhibitors, including volasertib and rigosertib, are currently undergoing clinical trials, showing promise in treating conditions like acute myeloid leukemia and myelodysplastic syndrome, with other inhibitors in earlier stages of development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Polo-Like Kinases: A Promising Therapeutic Approach for Cancer Treatment. Liu, X.[2020]

Polo-like kinase (PLK) inhibitors are being explored as a promising treatment for non-small cell lung cancer (NSCLC) due to their role in regulating cell proliferation and their frequent overexpression in tumors.

This review highlights the ongoing development of PLK inhibitors, focusing on their mechanisms of action, safety, and efficacy, as well as the search for biomarkers that could help identify which patients would benefit most from these targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers. Stratmann, JA., Sebastian, M.[2020]

In a phase I study involving 41 patients with relapsed/refractory non-Hodgkin lymphoma, the maximum tolerated dose (MTD) of the Plk1 inhibitor BI 2536 was determined to be 175 mg, with dose-limiting toxicities primarily being severe thrombocytopenia and neutropenia.

The study found that BI 2536 led to an overall response rate of 9.8%, with four patients showing responses, indicating potential efficacy of Plk1 inhibitors in treating certain types of cancer despite the challenges of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: a phase I, open-label, single dose-escalation study. Vose, JM., Friedberg, JW., Waller, EK., et al.[2023]

Polo-like kinases (PLKs) are overexpressed in about 80% of human tumors but are mostly absent in healthy tissues, making them a promising target for cancer therapies.

PLK inhibitors disrupt critical stages of cell division, leading to cancer cell death, and several of these inhibitors are currently in early clinical or advanced preclinical development, potentially offering new treatment options for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Schöffski, P.[2023]

The study identified the maximum tolerated dose (MTD) of NMS-1286937, a PLK1 inhibitor, as 24 mg/m2/day, with dose-limiting toxicities primarily involving hematological issues like thrombocytopenia and neutropenia.

Out of 21 patients with advanced solid tumors, disease stabilization was the best observed response, indicating potential antitumor activity, although further studies are needed to evaluate its efficacy more comprehensively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of NMS-1286937, an orally available Polo-Like Kinase 1 inhibitor, in patients with advanced or metastatic solid tumors. Weiss, GJ., Jameson, G., Von Hoff, DD., et al.[2023]

Polo-like kinase 1 (Plk1) is a key target in cancer treatment due to its overexpression in various cancer types, and inhibitors of Plk1 have shown significant therapeutic effects in pre-clinical and clinical studies.

Combination therapies using Plk1 inhibitors alongside other anticancer drugs have demonstrated synergistic effects, enhancing their overall anti-tumor efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments of polo-like kinase 1 (Plk1) inhibitors as anti-cancer agents. Li, S., Zhang, Y., Xu, W.[2023]

The Plk1 inhibitor BI_2536 effectively kills tumor cells both in laboratory settings and in living organisms, highlighting its potential as a cancer treatment.

In early clinical trials, BI_2536 was well tolerated by patients with advanced solid tumors and those with refractory or relapsed acute myeloid leukemia, showing promising antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BI_2536--targeting the mitotic kinase Polo-like kinase 1 (Plk1). Wäsch, R., Hasskarl, J., Schnerch, D., et al.[2023]

The trial established the maximum tolerated dose (MTD) of volasertib combined with cisplatin or carboplatin, finding that doses of 300 mg of volasertib with 100 mg/m² of cisplatin or AUC6 of carboplatin were safe and manageable for patients.

Partial responses were observed in four patients, and stable disease was achieved in 17 patients, indicating that the combination therapy shows potential efficacy in treating advanced solid tumors, even in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity. Awada, A., Dumez, H., Aftimos, PG., et al.[2023]

The maximum tolerated dose (MTD) of BI 2536, a specific inhibitor of polo-like kinase 1 (Plk1), was determined to be 200 mg in a phase I trial involving 40 patients with advanced solid tumors, with reversible neutropenia being the main dose-limiting toxicity.

BI 2536 demonstrated antitumor activity, with 23% of patients experiencing disease stabilization for 3 or more months, and it was generally well tolerated with a favorable pharmacokinetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation and pharmacokinetic study of BI 2536, a novel Polo-like kinase 1 inhibitor, in patients with advanced solid tumors. Mross, K., Frost, A., Steinbild, S., et al.[2023]

The study successfully demonstrated that silencing polo-like kinase 1 (Plk1) in adult mice can be achieved with minimal adverse effects, suggesting a potential model for evaluating drug toxicity.

In contrast to cancer cell lines, primary cells showed low dependency on Plk1 for proliferation and survival, indicating that Plk1 inhibitors may not be as effective in normal cells, which is crucial for predicting therapeutic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells. Raab, M., Kappel, S., Krämer, A., et al.[2023]

Polo-like kinases (Plks) are crucial for regulating the cell cycle, and their increased levels are linked to the development of various cancers.

Targeting Plks has shown promising results in preclinical studies for treating both solid tumors and blood cancers, indicating their potential as effective mitotic inhibitors in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polo-like kinase and its inhibitors: Ready for the match to start? Palmisiano, ND., Kasner, MT.[2023]

A new drug candidate, TAK-960, was developed as a PLK1 inhibitor using structure-based drug design, which is a method that helps in creating effective drugs by understanding the structure of target proteins.

TAK-960 is currently in Phase I clinical trials, meaning it is being tested for safety and dosage in adult patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). Nie, Z., Feher, V., Natala, S., et al.[2023]

The maximum tolerated dose (MTD) of BI 2536, a polo-like kinase (Plk)-1 inhibitor, was determined to be 100 mg per administration in a treatment schedule of days 1 and 8, while a 225 mg dose in a 24-hour infusion was well tolerated, indicating a favorable safety profile for further studies.

Among the 70 patients treated, 32% showed stable disease as a best overall response, suggesting that BI 2536 may have potential efficacy in managing advanced solid tumors, alongside manageable side effects like gastrointestinal issues and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors. Hofheinz, RD., Al-Batran, SE., Hochhaus, A., et al.[2023]

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