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Monomethyl Auristatin E Linked To A Sarcosine Decamer With A Beta-Alanine N-Terminus And Bcy9594 Via A Cleavable Linker

This article discusses ongoing clinical trials investigating the use of BT5528, a novel drug containing Monomethyl Auristatin E linked to a sarcosine decamer with a beta-alanine N-terminus and BCY9594 via a cleavable linker. The trials aim to evaluate the safety, effectiveness, and potential benefits of BT5528 in treating advanced solid tumors that express the EphA2 protein. The study includes both monotherapy and combination therapy with nivolumab, focusing on various cancer types such as urothelial, ovarian, lung, head and neck, breast, and gastrointestinal cancers.

Table of Contents

What is BT5528?

BT5528 is an innovative drug being developed to treat advanced solid tumors that express a protein called EphA2[1]. It’s also known by other names such as BCY6136[1]. The drug is made up of a powerful anti-cancer component called monomethyl auristatin E (MMAE) connected to a targeting molecule via a special link[1].

How Does BT5528 Work?

BT5528 works like a smart missile for cancer cells. The targeting part of the drug (BCY9594) helps it find cancer cells that have a lot of EphA2 protein on their surface. Once it reaches these cells, the link breaks, releasing the MMAE, which can then kill the cancer cells[1]. This targeted approach aims to attack cancer cells while minimizing damage to healthy cells.

What Conditions Does BT5528 Target?

BT5528 is being studied for treating various types of advanced solid tumors that express EphA2[1]. These may include:

  • Urothelial cancer (cancer of the bladder lining)
  • Ovarian cancer
  • Non-small cell lung cancer (NSCLC)
  • Head and neck cancer
  • Triple negative breast cancer (TNBC)
  • Gastric/upper gastrointestinal cancer

These types of cancers are known to often have high levels of EphA2 protein, making them potential targets for BT5528[1].

Current Clinical Trial

BT5528 is currently being studied in a Phase I/II clinical trial[1]. This trial aims to:

  1. Assess the safety and tolerability of BT5528
  2. Determine the right dose for future studies
  3. Look for early signs that the drug is working against tumors
  4. Study how the drug moves through and is processed by the body (pharmacokinetics)

The trial is divided into different parts:

  • Part A-1: Testing BT5528 alone
  • Part A-2: Testing BT5528 in combination with another immunotherapy drug called nivolumab
  • Part B: Further testing BT5528 alone in specific cancer types

Who Can Participate in the Trial?

The trial has specific criteria for who can participate. In general, patients must[1]:

  • Be at least 18 years old
  • Have advanced solid tumors that express EphA2
  • Have measurable disease
  • Have adequate organ function
  • Not have certain other health conditions that might interfere with the study

It’s important to note that there are additional specific criteria, and only a healthcare provider can determine if someone is eligible for the trial.

Potential Benefits and Risks

While BT5528 shows promise, it’s important to remember that it’s still in the testing phase. Potential benefits may include shrinking tumors or slowing cancer growth, but these are not guaranteed[1].

As with any experimental treatment, there may be risks and side effects. The trial is designed to carefully monitor patients for any adverse effects. Some areas of particular concern include[1]:

  • Effects on blood cells
  • Liver function
  • Heart rhythm
  • Potential for increased risk of bleeding or blood clots

Patients considering participating in this trial should discuss the potential risks and benefits thoroughly with their healthcare provider.

Aspect Details
Drug Name BT5528 (Monomethyl Auristatin E linked to a sarcosine decamer with a beta-alanine N-terminus and BCY9594 via a cleavable linker)
Trial Phase Phase I/II integrated trial
Target Conditions Advanced solid tumors expressing EphA2, including urothelial, ovarian, lung, head and neck, breast, and gastrointestinal cancers
Main Objectives Assess safety, tolerability, determine MTD and RP2D, evaluate preliminary clinical activity
Treatment Approaches BT5528 monotherapy and in combination with nivolumab
Key Endpoints Treatment-emergent adverse events, dose-limiting toxicities, objective response rate, duration of response, progression-free survival, overall survival
Eligibility Criteria Adults with advanced solid tumors, measurable disease, adequate organ function, available tumor tissue for analysis
Additional Assessments Pharmacokinetics of BT5528 and MMAE, anti-drug antibody development

FAQ

  • What is BT5528 and how does it work? BT5528 is a novel drug that contains Monomethyl Auristatin E linked to a sarcosine decamer with a beta-alanine N-terminus and BCY9594 via a cleavable linker. It is designed to target cancer cells that express the EphA2 protein, which is found in many advanced solid tumors. The drug aims to deliver its toxic payload specifically to cancer cells, potentially reducing side effects on healthy tissues.
  • What types of cancer are being studied in these clinical trials? The clinical trials are focusing on advanced solid tumors that express EphA2, including urothelial cancer, ovarian cancer, non-small cell lung cancer (NSCLC), head and neck cancer, triple-negative breast cancer (TNBC), and gastric/upper gastrointestinal cancer.
  • What are the main objectives of these clinical trials? The main objectives of these trials are to assess the safety and tolerability of BT5528, determine the maximum tolerated dose, identify the recommended Phase II dose, and evaluate the preliminary clinical activity of the drug. The studies also aim to assess the drug's effectiveness both as a monotherapy and in combination with nivolumab.
  • Who is eligible to participate in these clinical trials? Eligible participants are adults (18 years or older) with advanced solid tumors expressing EphA2, who have measurable disease and meet specific criteria for organ function and overall health. Patients must have available tumor tissue for analysis and be willing to comply with the study procedures. Some additional criteria may apply depending on the specific cohort.
  • What are some of the key outcomes being measured in these trials? The trials are measuring several key outcomes, including treatment-emergent adverse events, dose-limiting toxicities, objective response rate, duration of response, clinical benefit rate, time to tumor progression, progression-free survival, and overall survival. They are also assessing the pharmacokinetics of BT5528 and the development of anti-drug antibodies.

Ongoing Clinical Trials on Monomethyl Auristatin E Linked To A Sarcosine Decamer With A Beta-Alanine N-Terminus And Bcy9594 Via A Cleavable Linker

  • Study of BT5528 alone and with nivolumab in patients with advanced solid tumors that have EphA2 protein expression

    Not recruiting

    2 1 1 1
    Investigated drugs:
    Belgium Spain

Glossary

  • EphA2: A protein found on the surface of some cancer cells. It is often overexpressed in various types of advanced solid tumors and is the target of the drug BT5528 in these clinical trials.
  • Monomethyl Auristatin E (MMAE): A potent anti-cancer compound that interferes with cell division. In BT5528, it is linked to other components to create a targeted therapy for cancer cells expressing EphA2.
  • Cleavable linker: A chemical connection that can be broken under specific conditions. In BT5528, it allows the toxic MMAE to be released once the drug has reached its target cancer cells.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion. PK parameters help researchers understand how the body processes the drug.
  • Anti-drug antibody (ADA): Antibodies produced by the immune system in response to a therapeutic drug. The development of ADAs is monitored in clinical trials as they can potentially affect the drug's effectiveness or safety.
  • Maximum tolerated dose (MTD): The highest dose of a drug that can be given without causing unacceptable side effects. Determining the MTD is an important goal in early-phase clinical trials.
  • Recommended Phase II dose (RP2D): The dose of a drug determined to be appropriate for further testing in Phase II clinical trials, based on safety and preliminary efficacy data from earlier studies.
  • Objective response rate (ORR): The proportion of patients whose cancer shrinks (partial response) or disappears completely (complete response) after treatment. It is a key measure of a cancer drug's effectiveness.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without their cancer getting worse. PFS is an important indicator of a cancer treatment's effectiveness.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors version 1.1, a standardized set of rules used to measure how well a cancer patient responds to treatment in clinical trials.

References

  1. http://clinicaltrials.eu/trial/study-of-bt5528-and-nivolumab-for-patients-with-advanced-solid-tumors-expressing-epha2/