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

Ovarian Cancer Clinical Trial

Official 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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06433219
• Other study ID #: MS201924_0002
• Secondary ID: 2024-511202-23-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 26, 2024
• Est. completion date: January 25, 2028

Study information

• Verified date: April 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 25, 2028
• Est. primary completion date: January 10, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 (i.e. PARPi is the last treatment before study entry)

• 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.

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 last platinum administration in the second-line setting.

• History of additional malignancy within 3 years before the date of enrollment.

• Known brain metastases, unless clinically stable, i.e. 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.

• Other Protocol defined exclusion criteria.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Tuvusertib (M1774)
Tuvusertib will be administered orally
• Niraparib
Niraparib will be administered orally
• Lartesertib (M4076)
Lartesertib will be administered orally

Locations

Country	Name	City	State
Germany	Please Contact the Communication Center	Darmstadt
United States	Please Contact U.S. Medical Information	Rockland	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator		Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs		Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years.
Secondary	Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator		Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.
Secondary	Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator		Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.

External Links

•   Trial Awareness and Transparency website