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8-(1,3-Dimethylpyrazol-4-Yl)-1-(3-Fluoro-5-Methoxypyridin-4-Yl)-7-Methoxy-3-Methylimidazo[4,5-C]Quinolin-2-One

This article discusses a clinical trial investigating the use of a new drug combination for patients with advanced ovarian cancer who have previously been treated with PARP inhibitors. The study focuses on combining tuvusertib, an ATR inhibitor, with either niraparib (a PARP inhibitor) or lartesertib (an ATM inhibitor) to assess their efficacy and safety in treating epithelial ovarian cancer that has progressed despite prior PARP inhibitor therapy.

Table of Contents

Overview of Tuvusertib

Tuvusertib, also known as 8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methylimidazo[4,5-c]quinolin-2-one, is a promising new medication being studied for the treatment of advanced ovarian cancer[1]. It is specifically designed for patients whose cancer has progressed after previous treatment with a type of drug called a PARP inhibitor.

How Tuvusertib Works

Tuvusertib is classified as an ATR inhibitor. ATR stands for Ataxia Telangiectasia and Rad3-related protein, which is an important enzyme in the body that helps cancer cells repair their DNA and survive. By blocking this enzyme, tuvusertib may help prevent cancer cells from repairing themselves, potentially making them more vulnerable to other treatments[1].

Current Clinical Trial

A clinical trial called “DDRiver EOC 302” is currently underway to study tuvusertib in combination with other medications for patients with advanced ovarian cancer[1]. This trial is specifically for patients who have:

  • Epithelial ovarian cancer: This is the most common type of ovarian cancer, which starts in the cells that cover the outer surface of the ovary.
  • Cancer that has progressed after previous treatment with a PARP inhibitor: PARP inhibitors are a type of targeted therapy used in ovarian cancer treatment.
  • Certain genetic mutations: Specifically, mutations in genes called BRCA1 or BRCA2, or tumors with a characteristic called “homologous recombination deficiency” (HRD).

Eligibility Criteria

To participate in this study, patients must meet several criteria, including[1]:

  • Have confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancer that has come back after previous treatment.
  • Have tumors with specific genetic characteristics (BRCA mutations or HRD positive status).
  • Have experienced disease progression while on PARP inhibitor therapy, but have benefited from it for at least 6 months before the progression.
  • Have measurable disease according to specific criteria (RECIST v1.1).
  • Be in relatively good overall health, with an ECOG performance status of 0 or 1 (meaning they are able to carry out light to moderate physical activities).

There are also several factors that would exclude a patient from participating, such as having certain other medical conditions or a history of other cancers[1].

Study Design

The study is designed to test tuvusertib in combination with two other drugs[1]:

  1. Tuvusertib + Niraparib: Niraparib is a PARP inhibitor, which is already used in ovarian cancer treatment.
  2. Tuvusertib + Lartesertib: Lartesertib is an ATM inhibitor, another type of drug that affects how cancer cells repair their DNA.

Patients in the study will be randomly assigned to receive one of these combinations. The main goals of the study are to assess how effective these combinations are in treating the cancer and to evaluate their safety[1].

Potential Benefits and Risks

While tuvusertib shows promise, it’s important to remember that it is still being studied and its full effects are not yet known. Potential benefits could include shrinking tumors or slowing the progression of cancer. However, as with any medical treatment, there may also be risks and side effects[1].

The study will carefully monitor patients for any adverse effects. Some common side effects of cancer treatments can include fatigue, nausea, and changes in blood cell counts, but the specific side effects of tuvusertib are still being determined through this research[1].

Aspect Details
Study Type Open-label, multicenter, randomized Phase 2 study
Target Population Patients with advanced epithelial ovarian cancer that progressed on prior PARP inhibitor therapy
Intervention Tuvusertib combined with either Niraparib or Lartesertib
Primary Objectives 1. Assess efficacy (Objective Response)
2. Evaluate safety and tolerability
Key Inclusion Criteria – Confirmed high-grade serous or endometrioid ovarian cancer
– BRCA mutations or positive HRD status
– Disease progression on PARP inhibitor therapy
– Measurable disease per RECIST v1.1
Key Exclusion Criteria – Primary platinum-refractory disease
– Active brain metastases
– Active/uncontrolled infection
– History of organ transplantation
Primary Endpoints 1. Confirmed Objective Response
2. Number of participants with treatment-emergent adverse events

FAQ

  • What is the main purpose of this clinical trial? The main purpose of this trial is to assess the effectiveness and safety of combining tuvusertib with either niraparib or lartesertib in treating advanced ovarian cancer that has progressed after previous PARP inhibitor therapy. The study aims to determine which combination works best for further investigation.
  • Who is eligible to participate in this trial? Eligible participants are those with confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancer that has recurred. They must have specific genetic mutations (BRCA1 or BRCA2) or tumors with positive HRD status, and have experienced disease progression while on PARP inhibitor therapy.
  • How is the trial structured? The trial is an open-label, multicenter, randomized Phase 2 study. Participants will be randomly assigned to receive tuvusertib in combination with either niraparib or lartesertib. The study will assess the efficacy and safety of these combinations to determine which one should be further investigated in Part B of the trial.
  • What are the main outcomes being measured in this trial? The primary outcomes being measured are the confirmed objective response according to RECIST v1.1 criteria, as assessed by the investigator, and the number of participants experiencing treatment-emergent adverse events, serious adverse events, and related adverse events.
  • How will the study drugs be administered? All study drugs (tuvusertib, niraparib, and lartesertib) will be administered orally. The specific dosing regimens and schedules will be determined by the study protocol and may vary depending on which combination arm the participant is assigned to.

Ongoing Clinical Trials on 8-(1,3-Dimethylpyrazol-4-Yl)-1-(3-Fluoro-5-Methoxypyridin-4-Yl)-7-Methoxy-3-Methylimidazo[4,5-C]Quinolin-2-One

  • 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

Glossary

  • ATR inhibitor: A type of drug that blocks the activity of the ATR (Ataxia Telangiectasia and Rad3-related) protein, which is involved in DNA damage response. In this trial, tuvusertib is an ATR inhibitor.
  • PARP inhibitor: A class of drugs that block the activity of PARP (Poly (ADP-ribose) polymerase) enzymes, which are involved in DNA repair. Niraparib is a PARP inhibitor used in this trial.
  • ATM inhibitor: A type of drug that inhibits the ATM (Ataxia Telangiectasia Mutated) protein, which plays a role in DNA damage response. Lartesertib is an ATM inhibitor in this trial.
  • BRCA1 and BRCA2: Genes that produce tumor suppressor proteins. Mutations in these genes are associated with an increased risk of certain cancers, including ovarian cancer.
  • HRD (Homologous Recombination Deficiency): A condition where cells have difficulty repairing DNA damage through the homologous recombination pathway. This can make cancer cells more susceptible to certain treatments.
  • Epithelial ovarian cancer: A type of cancer that begins in the cells lining the ovaries or fallopian tubes. It is the most common form of ovarian cancer.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors version 1.1, a standard set of rules used to assess how well a cancer patient responds to treatment.
  • Open-label study: A type of clinical trial where both the researchers and participants know which treatment is being administered.
  • Randomized study: A study design where participants are randomly assigned to different treatment groups to reduce bias.
  • Phase 2 study: A stage of clinical research that focuses on evaluating the effectiveness and side effects of a treatment in a larger group of patients.

References

  1. http://clinicaltrials.eu/trial/study-of-tuvusertib-with-niraparib-or-lartesertib-for-patients-with-advanced-ovarian-cancer-after-previous-parp-inhibitor-treatment/