BTX-A51 for Liposarcoma

Recruiting at 2 trial locations

Overseen By Michael Wagner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Michael Wagner

Must not be taking: Investigational agents

Disqualifiers: Infection, CHF, Cirrhosis, CNS disease, others

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

Compensation: Varies

Number of Visits: 5

Duration: Until disease progression or unacceptable toxicity

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests BTX-A51, a new kinase inhibitor, to determine its safety and tolerability in people with certain types of liposarcoma (a rare cancer in fat cells) and CIC-rearranged sarcoma. The study involves two different doses of the treatment. It is suitable for those diagnosed with these specific sarcomas who have completed other cancer treatments but still experience the disease. Participants will undergo regular tumor biopsies and imaging scans to monitor the treatment's effects. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use other investigational or anticancer agents while participating in the trial, except for certain hormonal therapies for breast or prostate cancer.

Is there any evidence suggesting that BTX-A51 is likely to be safe for humans?

Research shows that BTX-A51, a type of drug, is under investigation for safety and tolerability in people with liposarcoma, a type of cancer. Earlier studies have found that this drug targets certain proteins that aid the growth of liposarcoma cells. Although extensive safety information from human trials is not yet available, lab tests have shown promising results.

Since this study is in its early stages, the main goal is to assess the drug's safety. Early studies often evaluate how well patients tolerate the treatment and document any side effects. While there is a strong scientific rationale for testing BTX-A51, researchers are still learning about its safety in humans. Participants in the trial will provide important safety information by trying two different doses of the drug. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

BTX-A51 is unique because it targets the molecular pathways involved in liposarcoma growth, which is different from traditional treatments like surgery, radiation, or chemotherapy that focus on removing or shrinking tumors. This treatment uses a targeted approach to potentially disrupt the cancer cells' ability to multiply. Researchers are excited about BTX-A51 because it offers a promising new way to tackle the disease at a cellular level, which could lead to more effective and less invasive treatment options for patients.

What evidence suggests that BTX-A51 might be an effective treatment for liposarcoma?

Research has shown that BTX-A51 may help treat liposarcoma, a type of cancer. Early lab studies found that BTX-A51 can be effective against liposarcoma cells by targeting proteins essential for cancer cell survival, including CK1α, CDK9, and CDK7. Positive results in lab settings suggest that BTX-A51 might help shrink tumors or slow their growth. This trial will evaluate different dosages of BTX-A51, specifically 21mg and 30mg, to determine its effectiveness in humans. While more research is needed, these early findings offer hope for people with liposarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael J Wagner, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with specific subtypes of liposarcoma that have spread or returned, and who haven't had cancer treatment in the last 14 days. They must be able to swallow pills, not be pregnant, agree to use two contraception methods during and after the study, have stable vital organ functions, and an ECOG performance status ≤2.

Inclusion Criteria

I am a woman able to have children and have a recent negative pregnancy test.

My organ and bone marrow functions meet the required levels for the study.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I cannot swallow pills or have issues absorbing medication.

Patient with current evidence of specific medical conditions that could compromise safety and/or assessment of efficacy

I do not have an active hepatitis B or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BTX-A51 3 times weekly in 28-day cycles, with tumor biopsies and radiologic imaging

Until disease progression or unacceptable toxicity

Day 1 of each 28-day cycle, radiologic imaging every 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• BTX-A51

Trial Overview The trial is testing BTX-A51 (a kinase inhibitor) for safety and tolerability in patients with liposarcoma. Participants will receive a recommended dose to see how well they handle it and if there are any beneficial effects on their condition.

How Is the Trial Designed?

Group I: BTX-A51 30mg Experimental Treatment 1 Intervention

Participants will be enrolled and will complete study procedures as follows: * Baseline visit with tumor biopsy. * Tumor biopsy at the end of Cycle 1. * Radiologic imaging every 2 cycles. * Cycle 1 through End of Treatment: --Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly. * End of Treatment visit with radiologic imaging. * Follow-up: every 3 months for 1 year.

Group II: BTX-A51 21mg Experimental Treatment 1 Intervention

Participants will be enrolled and will complete study procedures as follows: * Baseline visit with tumor biopsy. * Tumor biopsy at the end of Cycle 1. * Radiologic imaging every 2 cycles. * Cycle 1 through End of Treatment: --Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly. * End of Treatment visit with radiologic imaging. * Follow-up: every 3 months for 1 year.

Who Is Running the Clinical Trial?

Michael Wagner

Lead Sponsor

Trials

1

Recruited

10+

Michael Wagner, MD

Lead Sponsor

Trials

1

Recruited

10+

Edgewood Oncology Inc.

Industry Sponsor

Trials

3

Recruited

200+

Published Research Related to This Trial

Compound 24a is a newly developed covalent BTK inhibitor that shows strong inhibition of BTK activity with an IC50 of 4.0 nM and high selectivity over ITK and EGFR, reducing the risk of adverse effects associated with off-target inhibition.

In preclinical U-937 xenograft models, compound 24a significantly inhibited tumor growth by 57.85% at a dosage of 50 mg/kg, indicating its potential as an effective treatment for cancers involving BTK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of Pteridine-7(8H)-one Derivatives as Potent and Selective Inhibitors of Bruton's Tyrosine Kinase (BTK). Dou, D., Diao, Y., Sha, W., et al.[2022]

Targeted protein-tyrosine kinase inhibitors (PTKIs), like imatinib and gefitinib, are effective anticancer drugs that work by selectively inhibiting specific kinases involved in cancer development, with ongoing research into other PTKIs for various cancer types.

The success of PTKI therapy relies on identifying appropriate molecular targets for each patient, highlighting the need for advanced diagnostic tools to ensure effective treatment and to address issues of drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy. Smith, JK., Mamoon, NM., Duhé, RJ.[2019]

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]

In a study involving 12 healthy subjects, the new tablet (P22-TAB) and capsule (P22-CAP) formulations of CC-292, a BTK inhibitor, demonstrated similar or improved bioavailability compared to the original capsule formulation (P01-CAP).

All formulations were well tolerated at a 250 mg dose, indicating a favorable safety profile for CC-292 across different formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, phase 1, randomized, three treatments, three-period, crossover, relative bioavailability study of CC-292, a potent and orally available inhibitor of bruton tyrosine kinase. Cheng, Y., Liu, L., Xue, Y., et al.[2022]

The study identified new oxindole sulfonamide derivatives as promising inhibitors of Bruton's tyrosine kinase (BTK), which is crucial for the survival of B-cell malignancies like Burkitt's lymphoma.

Among the compounds tested, PID-4 demonstrated significant cytotoxicity against Burkitt's lymphoma cells while showing negligible effects on non-BTK cancerous and non-cancerous cell lines, indicating its potential as a targeted therapy with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Biological Evaluation of Oxindole Sulfonamide Derivatives as Bruton's Tyrosine Kinase Inhibitors. Koraboina, CP., Maddipati, VC., Annadurai, N., et al.[2023]

The combination of the Tyr-kinase inhibitors PP1 and GL-2003 effectively suppresses the growth of human pancreatic cancer xenografts in mice, showing similar efficacy to established treatments like gemcitabine.

This approach targets the PAK1 signaling pathway, which is crucial for RAS-induced cancer growth, suggesting a promising new therapeutic strategy for treating pancreatic cancer and potentially other cancers resistant to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors). Hirokawa, Y., Levitzki, A., Lessene, G., et al.[2014]

NRAS mutations are common in several cancers, including melanoma and acute myelogenous leukemia (AML), and have historically been difficult to target with therapies.

Recent developments in targeting the MAP/ERK kinase (MEK) pathway have shown promise, with MEK inhibitors demonstrating clinical efficacy as monotherapy and in combination with other agents, indicating a potential new approach for treating NRAS-mutant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular pathways: targeting NRAS in melanoma and acute myelogenous leukemia. Johnson, DB., Smalley, KS., Sosman, JA.[2022]

A series of novel compounds were developed as dual inhibitors of Btk and PI3Kδ kinases, showing effectiveness in suppressing leukemia cell proliferation at low micromolar concentrations in vitro.

Among these compounds, 16b demonstrated the strongest inhibitory activity against Btk and PI3Kδ, with IC50 values of 139 nM and 275 nM respectively, indicating its potential as a promising candidate for further development in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and synthesis of benzofuro[3,2-b]pyridin-2(1H)-one derivatives as anti-leukemia agents by inhibiting Btk and PI3Kδ. Liu, L., Shi, B., Li, X., et al.[2019]

Recent advancements have led to the development of small molecules that directly target the G12C mutant of oncogenic RAS proteins, which are implicated in about 24% of human cancers, marking a significant step in addressing previously considered 'undruggable' targets.

New strategies are emerging that not only focus on mutant RAS proteins but also consider the role of wild-type RAS and its interactions, suggesting that disrupting RAS activation pathways could be a viable therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RAS, wanted dead or alive: Advances in targeting RAS mutant cancers. Stalnecker, CA., Der, CJ.[2021]

In 2019, the FDA approved four new small molecule protein kinase antagonists (entrectinib, erdafitinib, pexidartinib, and fedratinib) that target specific genetic alterations in various cancers, demonstrating their efficacy in treating conditions like solid tumors and bladder cancers.

Overall, 52 small molecule protein kinase inhibitors have been approved, primarily for cancer treatment, with many showing effectiveness against multiple diseases, although resistance to these therapies remains a significant challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Roskoski, R.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06414434

NCT06414434 | BTX-A51 in Patients With Liposarcoma or ... This study is testing two different doses of BTX-A51 to determine if it is safe and tolerable in participants with liposarcoma with MDM2 amplification, myxoid ...

2. 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 ...

3. edgewoodoncology.com edgewoodoncology.com/news/edgewood-oncology-announces-positive-efficacy-data-from-investigator-sponsored-study-of-btx-a51-in-preclinical-models-of-liposarcoma-1

Edgewood Oncology Announces Positive Efficacy Data ... Edgewood Oncology Announces Positive Efficacy Data From Investigator-Sponsored Study of BTX-A51 in Preclinical Models of Liposarcoma.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06414434?term=mdm2&viewType=Table&rank=5

BTX-A51 in Patients With Liposarcoma or CIC-rearranged ... This study is testing two different doses of BTX-A51 to determine if it is safe and tolerable in participants with liposarcoma with MDM2 amplification, ...

5. edgewoodoncology.com edgewoodoncology.com/news/edgewood-oncology-announces-new-efficacy-data-from-investigator-sponsored-study-of-btx-a51-in-preclinical-models-of-liposarcoma

Edgewood Oncology Announces New Efficacy Data From ... Edgewood Oncology Announces New Efficacy Data From Investigator-Sponsored Study of BTX-A51 in Preclinical Models of Liposarcoma.

6. delta.larvol.com delta.larvol.com/Products/?ProductId=2332fd29-6dd1-4acc-954c-32a4b6595ee8

BTX-A51 / Edgewood Oncology Safety and efficacy of casein kinase 1α and cyclin dependent kinase 7/9 inhibition in patients with relapsed or refractory AML: A first-in-human study of BTX- ...