Tuvusertib in combination with Niraparib or Lartesertib in participants with epithelial ovarian carcinoma

Australia, Belgium, Denmark, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT06433219 (ICTRP)

Official title (approved by ethics committee)
An open-label, multicenter, randomized Phase 2 study of the ATR inhibitor tuvusertib in com-bination 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 (BASEC)

Academic 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 de?ciency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302) (ICTRP)

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

Disease under investigation
Ovarian Cancer (ICTRP)

Intervention under investigation
Drug: Tuvusertib (M1774)Drug: NiraparibDrug: Lartesertib (M4076) (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
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. (ICTRP)

not available

Primary and secondary end points
Part A and Part B: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator;Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs (ICTRP)

Part A and Part B: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator;Part A and Part B: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator;Part B: Overall Survival (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Merck KGaA, Darmstadt, Germany (ICTRP)

Additional contacts
Medical Responsible;US Medical Information, eMediUSA@emdserono.com, 888-275-7376, EMD Serono Research & Development Institute, Inc., (ICTRP)

Secondary trial IDs
2024-511202-23-00, MS201924_0002 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/study/NCT06433219 (ICTRP)