BTX-A51 for Cancer

Recruiting at 3 trial locations

Overseen By Zung Thai, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Edgewood Oncology Inc.

Must not be taking: Antineoplastics, Corticosteroids

Disqualifiers: CNS disease, Cardiac disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BTX-A51 (a casein kinase inhibitor), for individuals with advanced solid tumors unresponsive to standard treatments. The trial aims to determine a safe and promising dose for combating these cancers. In certain parts of the trial, BTX-A51 will be combined with fulvestrant to assess their combined effectiveness. Prospective participants should have an advanced solid tumor that has not improved with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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

The trial requires that you stop any local or systemic cancer treatments, including chemotherapy, hormonal therapy, or radiation, at least 3 weeks before starting the study drug. Chronic use of corticosteroids above a certain dose must also be stopped 4 weeks prior to the trial.

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

Research has shown that BTX-A51 was safe in earlier studies. In trials with patients who have relapsed or hard-to-treat acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), BTX-A51 was generally well-tolerated. Most side effects were not severe and could be managed with standard care.

Specific safety data on combining BTX-A51 with fulvestrant is limited. However, since BTX-A51 alone has been manageable, there is some confidence that this combination might also be well-tolerated. Fulvestrant, an FDA-approved drug commonly used in breast cancer treatments, has a well-known safety profile.

Overall, these findings suggest that BTX-A51, both alone and with fulvestrant, has a manageable safety profile based on current data. However, individual experiences can vary, and participating in a clinical trial will involve close monitoring for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BTX-A51 for cancer because it offers a novel approach compared to standard treatments like chemotherapy, targeted therapy, or hormonal therapy. BTX-A51 is unique in its mechanism, as it targets specific pathways in cancer cells, potentially leading to more effective treatment with fewer side effects. Additionally, the combination of BTX-A51 with fulvestrant, a well-known hormone therapy, in one of the trial's arms could enhance the effectiveness against hormone receptor-positive cancers. This innovative approach could provide a new line of attack against cancer, offering hope for improved outcomes.

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

Research has shown that BTX-A51 is promising because it blocks certain enzymes that help cancer cells grow. It specifically targets enzymes like Casein Kinase 1α (CK1α) and others involved in cell division. Early lab studies demonstrated that BTX-A51 works well before human testing. In this trial, some participants will receive BTX-A51 with fulvestrant, which may improve treatment by affecting more cancer cell pathways. Initial trials indicated it is generally safe, making it a strong candidate for further cancer research. ^{1 2 4 5 6}

Who Is on the Research Team?

Zung Thai, MD

Principal Investigator

Edgewood Oncology Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors or B cell Non-Hodgkin Lymphoma that's resistant to standard treatments can join. They must have measurable disease, not be pregnant, agree to use contraception, and have good organ function. Those with MYC amplified/overexpressed tumors are eligible for the expansion phase.

Inclusion Criteria

Demonstration of understanding and voluntarily signing of an informed consent form

My organs are functioning well.

My cancer can be measured using scans.

Exclusion Criteria

Life expectancy <3 months, as determined by the Investigator

I haven't taken more than 10 mg of steroids daily in the last month.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a (Dose Escalation Phase)

Determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of BTX-A51

4 weeks

Weekly visits for dosing and monitoring

Phase 1b (Monotherapy Dose Ranging Phase)

Evaluate safety and preliminary efficacy of BTX-A51 in subjects with ER+, HER2- metastatic breast cancer

4 weeks

Weekly visits for dosing and monitoring

Phase 1c (Combination Safety Phase)

Evaluate the safety and tolerability of BTX-A51 combined with fulvestrant

4 weeks

Weekly visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BTX-A51

Trial Overview The trial is testing BTX-A51, an oral drug given on a weekly schedule (5 days on/2 days off). It has two phases: Phase 1a finds the safest dose by slowly increasing amounts; Phase 1b expands this dose to more patients focusing on those with specific genetic tumor features.

How Is the Trial Designed?

Group I: BTX-A51 in Combination with Fulvestrant Cohort 2 Experimental Treatment 1 Intervention

Up to 2-times the SD of BTX-A51 administered orally 3 times per week in a 28-day cycle; fulvestrant administered as a 500-mg intramuscular injection on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles.

Group II: BTX-A51 in Combination with Fulvestrant Cohort 1 Experimental Treatment 1 Intervention

Starting dose (SD) of BTX-A51 administered orally 3 times per week in a 28-day cycle; fulvestrant administered as a 500-mg intramuscular injection on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles.

Group III: BTX-A51 Dose Cohort 6 Experimental Treatment 1 Intervention

Up to 10-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle

Group IV: BTX-A51 Dose Cohort 5 Experimental Treatment 1 Intervention

Up to 7-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle

Group V: BTX-A51 Dose Cohort 4 Experimental Treatment 1 Intervention

Up to 5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle

Group VI: BTX-A51 Dose Cohort 3 Experimental Treatment 1 Intervention

Up to 3.5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle

Group VII: BTX-A51 Dose Cohort 2 Experimental Treatment 1 Intervention

Up to 2-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle

Group VIII: BTX-A51 Dose Cohort 1 Experimental Treatment 1 Intervention

Starting dose (SD) of BTX-A51 administered orally 5 times per week in a 28-day cycle

Who Is Running the Clinical Trial?

Edgewood Oncology Inc.

Lead Sponsor

Trials

3

Recruited

200+

BioTheryX, Inc.

Lead Sponsor

Trials

3

Recruited

200+

Published Research Related to This Trial

Bruton's tyrosine kinase (BTK) has become a key target for developing new therapies for cancer and autoimmune disorders, with five irreversible BTK inhibitors already available on the market.

Recent research highlights the potential of reversible BTK inhibitors, which may have fewer side effects and be more suitable for long-term use in autoimmune conditions, along with new tunable irreversible inhibitors and PROTAC molecules that could enhance treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Development of BTK Inhibitors: A Five-Year Update. Tasso, B., Spallarossa, A., Russo, E., et al.[2022]

CX-4945 is the first orally bioavailable small molecule inhibitor of casein kinase 2 (CK2), which plays a significant role in cancer cell proliferation and tumor progression.

In preclinical studies, CX-4945 demonstrated anti-proliferative effects by inhibiting the cell cycle and the PI3K/Akt signaling pathway, while also reducing angiogenesis and inflammation in breast cancer cells, suggesting its potential as an effective anti-cancer treatment in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Druggability of the CK2 inhibitor CX-4945 as an anticancer drug and beyond. Kim, J., Kim, SH.[2021]

The study found that CK2 inhibitors (DMAT, MPT, AEAT) combined with pentabromobenzylisothioureas (ZKK-3, ZKK-9, ZKK-13) produced a synergistic pro-apoptotic effect against the KG-1 acute myelogenous leukemia cell line, indicating a promising treatment strategy.

Among the CK2 inhibitors tested, AEAT showed the highest apoptotic activity, suggesting it may be the most effective option for targeting leukemia cells in this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic anti-leukemic effects of CK2 inhibitors and pentabromobenzylisothioureas in vitro. Koronkiewicz, M., Chilmonczyk, Z., Kazimierczuk, Z.[2014]

Hematein, a novel CK2 inhibitor, effectively suppressed lung cancer cell growth and induced apoptosis in a murine xenograft model without causing significant toxicity to the mice.

Molecular docking studies revealed that hematein binds to CK2α at durable sites, indicating its role as an allosteric inhibitor of protein kinase CK2, which contributes to its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model. Hung, MS., Xu, Z., Chen, Y., et al.[2021]

The study found that tetra-bromo-cinnamic acid (TBCA), a selective CK2 inhibitor, effectively reduced cell proliferation and induced G2/M cell cycle arrest in prostate cancer cell lines, suggesting its potential as a therapeutic agent.

TBCA was shown to block the nuclear translocation of the androgen receptor (AR) and inhibit AR-mediated gene expression, indicating that CK2 subunits α and α' play a significant role in AR signaling in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells. Yao, K., Youn, H., Gao, X., et al.[2012]

A new PROTAC molecule, 15-271, was developed to target BTK and shows improved solubility and bioavailability compared to ibrutinib, which is important for treating B-cell malignancies.

15-271 also demonstrates better liver microsomal stability and a longer half-life in vivo, suggesting it could be a more effective treatment option for patients with BTKC481S mutation-induced drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo. Sun, Y., Yang, Z., Zhang, Z., et al.[2023]

Two new inhibitors targeting casein kinase 1δ/ε were developed, showing low nanomolar potency in reducing the growth of MDA-MB-231 triple negative breast cancer cells in laboratory tests.

These inhibitors also demonstrated favorable pharmacokinetic properties, making them suitable for further testing in animal models to evaluate their effectiveness against human cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer. Monastyrskyi, A., Nilchan, N., Quereda, V., et al.[2021]

UBX-382, a novel proteolysis-targeting chimera (PROTAC), effectively degrades both wild-type and mutant Bruton tyrosine kinase (BTK) proteins, showing strong potential for treating B-cell lymphomas with a half-maximal degradation concentration in the single-digit nanomolar range.

In murine xenograft models, UBX-382 led to complete tumor regression after less than 2 weeks of oral dosing, outperforming other BTK inhibitors like ibrutinib, indicating its promising efficacy in targeting B-cell-related blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models. Lim, YS., Yoo, SM., Patil, V., et al.[2023]

The combination of AT-101 and topotecan was found to be safe for patients with relapsed and refractory small cell lung cancer (SCLC), with a recommended dose of 40 mg AT-101 and 1.25 mg/m² topotecan.

Although the study did not meet the predefined response rate criteria for further enrollment, many patients experienced stable disease, and the median time to progression was 17.4 weeks for sensitive-relapsed patients and 11.7 weeks for refractory patients, suggesting potential benefits in disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer. Heist, RS., Fain, J., Chinnasami, B., et al.[2013]

Bruton's tyrosine kinase (BTK) inhibitors, already approved by the FDA, show promise as new treatments for patients with solid tumors that are resistant to traditional chemotherapy.

Emerging evidence suggests that BTK inhibitors could be combined with other therapies to create effective treatment regimens for metastatic and therapy-refractory solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Solid Tumors With BTK Inhibitors. Uckun, FM., Venkatachalam, T.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40665325/

Phase I first-in-human dose escalation study of the oral casein ... Here, we report on the results of the phase 1 clinical trial of BTX A51 in patients with relapsed or refractory AML and MDS.

2. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01724-z

Phase I first-in-human dose escalation study of the oral casein ... BTX A51 is an oral multi-kinase inhibitor having a unique set of target enzymes; it is a direct inhibitor of Casein Kinase 1α (CK1α) and cyclin ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7030

A first-in-human study of BTX-A51. Here, we report the interim results of the first-in-human (FIH) study of BTX-A51 in patients (pts) with R/R AML. Methods: The study utilizes a ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/2980/756804/Abstract-2980-Therapeutic-potential-of-combined

Therapeutic potential of combined targeting of casein kinase 1 ... Conclusions: These data have confirmed CK1α, CDK9, and CDK7 as essential for LPS cells and indicate that BTX-A51 has potent preclinical efficacy ...

5. targetedonc.com targetedonc.com/view/btx-a51-demonstrates-tolerability-and-manageable-safety-profile-in-patients-with-r-r-aml-mds

BTX A51 Demonstrates Tolerability and Manageable ... The oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 revealed a manageable safety profile in relapsed or refractory ...

6. withpower.com withpower.com/trial/btx-a51-for-cancer-85994

BTX-A51 for Cancer There is limited safety data specifically for BTX-A51, but similar CK2 inhibitors like hematein have shown to inhibit tumor growth in mice without significant ...