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NCT Number: NCT06433219

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

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 and to assess any differences between tuvusertib monotherapy and combination therapy. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objectives of this study are to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse and safety in terms of adverse events.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.
  • Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening.
  • Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be >6 months, with documented disease progression prior to study entry).

OR Progression on second-line maintenance PARPi: Participants are not allowed any additional systemic anticancer treatments before study entry (that is PARPi is the last treatment before study entry)

  • Intolerant to standard of care treatment options or refused standard of care treatment or the participant's treating physician considers that the lack of standard of care treatment is not detrimental for the participant.
  • Measurable disease per RECIST v1.1, as assessed by Investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
  • Other Protocol defined inclusion criteria could apply.

Exclusion criteria

  • Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the platinum administration in either the first or second-line setting.
  • History of additional malignancy within 3 years before the date of enrollment.
  • Known brain metastases, unless clinically stable, that is without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration.
  • Active and/or uncontrolled infection.
  • History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.
  • Organ transplantation, including allogenic stem cell transplant.
  • Patients with history of drug-induced severe cutaneous adverse reaction (SCAR; including but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], or drug reaction with eosinophilia and systemic symptoms [DRESS]), or dose-limiting immune-mediated reactions related to skin.
  • Other Protocol defined exclusion criteria could apply.

Treatment and study plan

Tuvusertib (M1774)

Drug

Tuvusertib will be administered orally.

Other names: M1774, VXc-400, VRT-1363004, substance code MSC2584415A

Niraparib

Drug

Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.

Other names: GSK3985771, MK-4827

Lartesertib (M4076)

Drug

Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib

Other names: M4076, substance code MSC2585823A

Primary outcomes

  1. Part A and Part B: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator

    Time frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years

  2. Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs

    Time frame: Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years

Secondary outcomes

  1. Part A and Part B: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator

    Time frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years

  2. Part A and Part B: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator

    Time frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years

  3. Part B: Overall Survival

    Time frame: Time from date of randomization to death, approximately 3.5 years

    OS is defined as the time from randomization to death due to any cause.

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study title

An Open-label, Multicenter, Randomized Phase 2 Study of the ATR Inhibitor Tuvusertib in Combination With the PARP Inhibitor Niraparib or the ATM Inhibitor Lartesertib in Participants With BRCA Mutant and/or Homologous Recombination deficiency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302)

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
May 29, 2024
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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