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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

31 Oct 2024 → ongoing

Decision date (initial)

2024-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic

Part A: To assess efficacy in terms of OR for the combination of tuvusertib with niraparib and the combination of tuvusertib with lartesertib, to support selection of best combination for Part B
Part A: To evaluate the safety and tolerability for the combination of tuvusertib with niraparib and the combination of tuvusertib with lartesertib to support selection of best combination for Part B
Part B: To assess efficacy in terms of OR for the 2 dose levels of tuvusertib combination regimen selected in Part A and tuvusertib monotherapy in order to assess the difference between monotherapy and combination and to inform selection of RP2D of tuvusertib combination
Part B: To evaluate the safety and tolerability for the 2 dose levels of tuvusertib combination regimen selected in Part A and tuvusertib monotherapy

Conditions and MedDRA coding

Epithelial ovarian cancer that progressed on prior PARP inhibitor therapy

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.
2. 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.
3. 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)
4. 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.
5. Measurable disease per RECIST v1.1, as assessed by Investigator.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
7. Other Protocol defined inclusion criteria.

Exclusion criteria 8

1. 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
2. History of additional malignancy within 3 years before the date of enrollment.
3. 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.
4. Active and/or uncontrolled infection
5. History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.
6. Organ transplantation, including allogenic stem cell transplant.
7. 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.
8. Other Protocol defined exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 3

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 5

Locations

8 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 267 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications