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2-Amino-6-Fluoro-N-(5-Fluoro-4-(1-Methyl-1H-Imidazol-5-Yl)Pyridin-3-Yl)Pyrazolo[1,5-A]Pyrimidine-3-Carboxamide

This article summarizes clinical trials investigating the use of tuvusertib (M1774), an ATR inhibitor, in combination with other therapies for treating advanced cancers. The trials focus on non-small cell lung cancer, breast cancer, and ovarian cancer that have progressed after previous treatments. Researchers are evaluating tuvusertib’s safety, efficacy, and potential to overcome resistance to other targeted therapies.

Table of Contents

What is Tuvusertib?

Tuvusertib is an experimental cancer drug that is currently being studied in clinical trials. Its scientific name is 2-amino-6-fluoro-N-(5-fluoro-4-(1-methyl-1H-imidazol-5-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. It is also known by other names like M1774, VXc-400, and MSC2584415A.[1]

Tuvusertib comes in the form of capsules that are taken by mouth. It is being developed as a potential new treatment option for patients with advanced cancers that have stopped responding to other therapies.

How Does Tuvusertib Work?

Tuvusertib is a type of drug called an ATR inhibitor. ATR stands for “ataxia telangiectasia and Rad3-related protein”. This protein plays an important role in helping cancer cells repair damage to their DNA and continue growing.[2]

By blocking the ATR protein, tuvusertib aims to make it harder for cancer cells to repair DNA damage. This can potentially make the cancer cells more vulnerable to dying or being killed by other cancer treatments.

Cancers Being Studied

Clinical trials are currently evaluating tuvusertib for several types of advanced cancers, including:

  • Non-small cell lung cancer (NSCLC) – A common type of lung cancer[1]
  • Breast cancer – Specifically hormone receptor-positive, HER2-negative advanced breast cancer[2]
  • Ovarian cancer – Including ovarian, fallopian tube, and primary peritoneal cancers[3]

The trials are focusing on patients whose cancers have progressed after receiving other standard treatments like chemotherapy, targeted therapies, or immunotherapy.

Clinical Trials

Several clinical trials are currently ongoing to evaluate tuvusertib:

  • A phase 1b/2a trial combining tuvusertib with an immunotherapy drug called cemiplimab in patients with advanced non-small cell lung cancer[1]
  • A phase 1/2 study of tuvusertib plus fulvestrant (a hormone therapy) for advanced breast cancer[2]
  • A phase 2 trial testing tuvusertib in combination with either niraparib or lartesertib for advanced ovarian cancer[3]

These trials aim to determine the safety, proper dosing, and effectiveness of tuvusertib alone or combined with other cancer drugs. They are recruiting patients whose cancers have specific genetic features or have stopped responding to previous treatments.

Potential Benefits

While it’s still too early to know for sure, researchers hope tuvusertib may offer several potential benefits:

  • A new treatment option for cancers that have become resistant to other therapies
  • Possible improved effectiveness when combined with other cancer drugs
  • A different mechanism of action compared to existing treatments
  • Oral administration, allowing patients to take it at home

However, more research is needed to confirm if tuvusertib will provide these benefits. The ongoing clinical trials will help determine how well it works and for which patients.

Side Effects and Safety

As tuvusertib is still in clinical trials, its full safety profile is not yet known. The current studies are closely monitoring patients for any side effects or safety issues. Common side effects of cancer treatments can include fatigue, nausea, decreased blood cell counts, and increased risk of infections.

Patients in the trials undergo regular check-ups and tests to monitor for any problems. The researchers will use this information to determine the safest and most effective doses of tuvusertib.

Future Directions

The development of tuvusertib is still in relatively early stages. If the current clinical trials show promising results, larger studies may be conducted to further evaluate its effectiveness and safety. Researchers are also interested in identifying which patients are most likely to benefit from this treatment.

Future studies may explore using tuvusertib for other types of cancer or in different combinations with existing therapies. The goal is to find new ways to help patients with advanced cancers that have limited treatment options.

Trial Name Cancer Type Combination Therapy Key Eligibility Primary Endpoints
DDRiver NSCLC 322 Non-squamous non-small cell lung cancer Tuvusertib + Cemiplimab Progressed on anti-PD-(L)1 and platinum therapy Objective response, Safety
MATRIX-IPC 2022-029 HR+/HER2- advanced breast cancer Tuvusertib + Fulvestrant Resistant to CDK4/6 inhibitor + aromatase inhibitor Maximum tolerated dose, Clinical benefit rate
DDRiver EOC 302 Epithelial ovarian cancer Tuvusertib + Niraparib or Lartesertib BRCA mutant and/or HRD+, progressed on PARP inhibitor Objective response, Safety

FAQ

  • What is tuvusertib? Tuvusertib (also known as M1774) is an ATR inhibitor drug being studied for treating advanced cancers. It works by blocking a protein called ATR that helps cancer cells repair DNA damage and survive.
  • What types of cancer are being studied with tuvusertib? The clinical trials are studying tuvusertib for advanced non-small cell lung cancer, hormone receptor-positive breast cancer, and epithelial ovarian cancer that have progressed after previous treatments.
  • How is tuvusertib given to patients? Tuvusertib is given orally as a capsule. The exact dosing regimens are being determined in the phase 1 parts of the trials.
  • What other drugs is tuvusertib being combined with? Tuvusertib is being studied in combination with drugs like cemiplimab (for lung cancer), fulvestrant (for breast cancer), and niraparib or lartesertib (for ovarian cancer).
  • What are the main goals of these clinical trials? The main goals are to determine the safety, tolerability, and effectiveness of tuvusertib combinations. Researchers are looking at tumor response rates, progression-free survival, and overall survival in patients with advanced cancers.

Ongoing Clinical Trials on 2-Amino-6-Fluoro-N-(5-Fluoro-4-(1-Methyl-1H-Imidazol-5-Yl)Pyridin-3-Yl)Pyrazolo[1,5-A]Pyrimidine-3-Carboxamide

  • Study of tuvusertib combined with niraparib or lartesertib for patients with ovarian cancer that worsened after previous PARP inhibitor treatment

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Denmark France Germany Italy The Netherlands +2

  • Study of Tuvusertib and Cemiplimab for Patients with Non-Squamous Non-Small Cell Lung Cancer After Previous Treatments

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium France Germany Italy Spain

Glossary

  • ATR inhibitor: A type of drug that blocks the ATR protein, which helps cancer cells repair DNA damage. By inhibiting ATR, these drugs aim to make cancer cells more vulnerable to DNA-damaging treatments.
  • RECIST: Response Evaluation Criteria in Solid Tumors. A standard way to measure how well a cancer patient responds to treatment based on changes in tumor size.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without their cancer getting worse.
  • Overall survival (OS): The length of time from the start of treatment that patients are still alive.
  • Objective response (OR): When a tumor shrinks or disappears after treatment, as measured by imaging tests.
  • PARP inhibitor: A type of targeted therapy that blocks the PARP enzyme, making it harder for cancer cells to repair DNA damage.
  • HER2-negative: Breast cancers that do not have high levels of a protein called HER2 on the surface of the cancer cells.
  • Hormone receptor-positive: Breast cancers that have receptors for estrogen or progesterone, which can promote cancer growth.
  • Homologous recombination deficiency (HRD): A defect in a cell's ability to repair certain types of DNA damage, which can make cancers more sensitive to some treatments.
  • BRCA mutations: Changes in the BRCA1 or BRCA2 genes that increase cancer risk and can affect how tumors respond to certain treatments.

References

  1. http://clinicaltrials.eu/trial/study-of-tuvusertib-and-cemiplimab-for-patients-with-non-squamous-non-small-cell-lung-cancer-after-previous-treatments/
  2. http://clinicaltrials.eu/trial/study-of-tuvusertib-and-fulvestrant-for-advanced-breast-cancer-resistant-to-cdk4-6-and-aromatase-inhibitors-in-hormone-receptor-positive-her2-negative-patients/
  3. http://clinicaltrials.eu/trial/study-of-tuvusertib-with-niraparib-or-lartesertib-for-patients-with-advanced-ovarian-cancer-after-previous-parp-inhibitor-treatment/