Tuvusertib + Niraparib/Lartesertib for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+61 other locations
Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: EMD Serono Research & Development Institute, Inc.
Disqualifiers: Platinum-refractory, Recent malignancy, Brain metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to measure the effect and safety of treatment with tuvusertib combined with either niraparib or lartesertib in participants with epithelial ovarian cancer. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objective of the study is to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should have progressed on PARP inhibitors before joining, which suggests that you may need to stop those specific medications. It's best to discuss your current medications with the trial coordinators.
What data supports the effectiveness of the drug combination Tuvusertib + Niraparib/Lartesertib for ovarian cancer?
Research shows that niraparib, one of the drugs in the combination, has been effective in extending the time without cancer progression in patients with ovarian cancer, regardless of certain genetic mutations. This suggests that niraparib can be beneficial in treating ovarian cancer.
12345Is the combination of Tuvusertib and Niraparib/Lartesertib safe for humans?
Niraparib has been studied for safety in various trials for ovarian cancer, showing it can be used safely as a maintenance treatment, although specific side effects and safety profiles should be discussed with a healthcare provider.
46789What makes the drug Tuvusertib + Niraparib/Lartesertib unique for ovarian cancer?
Tuvusertib combined with Niraparib or Lartesertib is unique because it explores a novel combination of drugs that may offer new treatment avenues for ovarian cancer, especially in cases where traditional platinum-based therapies are not effective. Niraparib, a PARP inhibitor, is already known for its use in maintenance therapy for ovarian cancer, and combining it with Tuvusertib could enhance its effectiveness by targeting different pathways involved in cancer cell survival.
1341011Eligibility Criteria
This trial is for individuals with epithelial ovarian cancer who have previously not responded well to treatment with a PARP inhibitor. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions or treatments.Inclusion Criteria
My tumor has harmful BRCA1/2 mutations or is HRD positive.
My cancer progressed after first-line PARPi treatment, and I've had only one platinum-based chemotherapy before this study.
I have not received any cancer treatments after my second-line PARPi therapy.
My cancer is a high-grade serous or endometrioid type that has come back.
I have seen improvement with PARPi treatment before my cancer progressed.
I am mostly active and my doctor expects me to live at least 6 more months.
My cancer progressed while on PARP inhibitors.
Exclusion Criteria
I do not have any active or uncontrolled infections.
My brain metastases are stable.
I have had an organ or stem cell transplant.
My cancer did not respond to initial platinum-based chemotherapy.
Participant Groups
The study tests the effectiveness and safety of tuvusertib in combination with either niraparib or lartesertib in those with epithelial ovarian cancer. It aims to see if these combinations can reduce tumor size or stop tumor growth after previous treatments haven't worked.
2Treatment groups
Experimental Treatment
Group I: Tuvusertib with NiraparibExperimental Treatment2 Interventions
Group II: Tuvusertib with LartesertibExperimental Treatment2 Interventions
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Next Oncology - VirginiaFairfax, VA
Memorial Sloan Kettering Cancer CenterNew York, NY
Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIMENew York, NY
Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) - Ospedale S.GiovannLittle Rock, AR
More Trial Locations
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Who is running the clinical trial?
EMD Serono Research & Development Institute, Inc.Lead Sponsor
Merck KGaA, Darmstadt, GermanyIndustry Sponsor
References
Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects. [2023]In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS.
Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial. [2023]The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease.
Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. [2022]This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer.
OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. [2022]To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.
In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma. [2023]Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo.
Niraparib and Advanced Ovarian Cancer: A Beacon in the Non-BRCA Mutated Setting. [2023]Ovarian cancer (OC) is the eighth most common cancer among the female population and the most lethal of all the female reproductive system malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have reshaped the treatment scenario of metastatic OC in the maintenance setting post platinum-based chemotherapy. Niraparib is the first Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved PARPi as maintenance therapy for platinum-sensitive OC, regardless of BReast CAncer gene (BRCA) status, in first-line patients, with a recent restriction to germline BRCA mutations in second-line patients. In this review, we comprehensively summarized the pharmacological properties of niraparib, alongside the efficacy and safety data of the main trials leading to the current approvals, and discussed the future development of this agent.
Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. [2021]To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. [2020]This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer.
Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. [2019]To analyze the safety and efficacy of niraparib in patients aged ≥70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial.
Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. [2022]Combined navicixizumab and paclitaxel showed durable activity in patients with platinum-resistant ovarian cancer.
Niraparib in the maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: safety and efficacy. [2022]Introduction: Approximately 300,000 women worldwide are diagnosed each year with ovarian cancer. Frequently diagnosed in late stages with ambiguous symptomatology, ovarian cancer has a low survival rate.Areas covered: Niraparib, a PARP inhibitor, was approved in 2020 for use in the maintenance treatment of ovarian cancer regardless of biomarker status. Included in the review are PRIMA (NCT02655016), NOVA (NCT01847274), AVANOVA2 (NCT02354131), and QUADRA (NCT02354586) trials which herald the advent of using maintenance oral therapies in the treatment of ovarian cancer. Additionally, with new combination drug trials, exciting avenues for treatment are also discussed with the FIRST (NCT03016338) trial.Expert opinion: Maintenance niraparib treatment regardless of genetic profile offers a new modality for the treatment of ovarian cancer with a low side effect profile and importantly oral dosing. New combinations of synergistic immunotherapeutics, and antiangiogenesis therapies with niraparib also offer exciting new frontiers for patients with ovarian cancer.