Condition(s):Advanced Solid Tumors (Excluding Prostate Cancer), Ovarian Cancer
Principal Investigator:Konstantinopoulos, Panagiotis, A.
Site Research Nurse(s):Belavusava, Vera,
The purpose of the study is to test how well patients with advanced solid tumors and ovarian
cancer respond to treatment with elimusertib in combination with niraparib. In addition
researchers want to find for patients the optimal dose of elimusertib in combination with
niraparib, how the drug is tolerated and the way the body absorbs, distributes and discharges
the drug. The study medication elimusertib works by blocking a substance produced by the body
(ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a
substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or
made more susceptible to chemotherapy.
- Participant must be ≥ 18 years of age, at the time of signing the informed consent.
- Participants must have histologically confirmed diagnosis of the following indications
as described below:
- Dose escalation (Part A): recurrent advanced solid tumors, excluding prostate
cancer, who experienced disease progression after treatment with standard of care
therapy for metastatic disease.
- Dose expansion (Part B): recurrent EOC, fallopian tube or primary peritoneal
- Sub-population 1: participants PARPi naïve and with a
platinum-resistant/refractory disease (recurrence with a PFI < 6 months from
last platinum-based regimen). Participants may not have had more than 3
prior therapies since the development of platinum resistance.
- Sub-population 2: participants with disease progression on PARPi (including
niraparib), administered as maintenance as well active line of therapy.
Participants must have not received further line of therapy after disease
progression on PARPi.
- Participants in dose escalation (Part A) of the study will need to have
tumor-associated DDR deficiency and/or CCNE1 gene amplification.
-- A homozygous deletion and/or a deleterious mutation in a gene reported to be
involved in DNA repair and/or sensitive to ATRi's and/or PARPi's.
- Participants in dose expansion (Part B) of the study will need to have tumor
associated DDR deficiency (Sub-population 1). Participants in Part B (Sub-population
2) are not enrolled based on the presence or absence of a particular biomarker.
- Participants must have disease progression and measurable disease, as defined by
- Available archival tumor tissue ≤ 12 months old, otherwise a fresh baseline tumor
biopsy should be obtained.
- ECOG PS of 0 to 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow function as assessed by the following laboratory tests to be
conducted within 7 (±2) days before the first dose of study intervention:
- Hemoglobin (Hb) ≥ 10 g/dL
- Platelet count ≥ 150 x 10^9/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Participants must have adequate organ function.
- Participants must have adequate coagulation.
- Adequate cardiac function per institutional normal measured by echocardiography
(recommended) or cardiac MRI per institutional guidelines.
- A female participant is eligible to participate if she is not pregnant (confirmed by a
negative serum pregnancy test within 7 (±2) days of first study intervention), not
breastfeeding, or is not a woman of childbearing potential (WOCBP). WOCBP must agree
to use highly effective contraception during the intervention period and for at least
6 months (180 days) after the last dose of study intervention.
- Inability to swallow oral medication
- Known hypersensitivity to elimusertib and/or niraparib or excipients of the
preparations or any agent given in association with this study
- History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
- Ongoing or active uncontrolled infection (bacterial, fungal, or viral; e.g. hepatitis
viral) of CTCAE grade ≥ 2 that requires systemic treatment
- Participants with HIV may be be ineligible depending on various parameters, but are
not automatically excluded.
- Immunocompromised participants (e.g. diagnosis of immunodeficiency or ongoing
- Pleural effusion or ascites that causes respiratory compromise (CTCAE grade ≥ 2
- Active HBV or HCV infection that requires treatment.
- Moderate or severe hepatic impairment, i.e. Child Pugh Class B or C
- Participants with significant cardiovascular disease and/or relevant findings meeting
the below criteria are excluded:
- History of cardiac disease: congestive heart failure NYHA class > II, unstable
angina (angina symptoms at rest), new-onset angina (within the past 6 months
before study entry), myocardial infarction within the past 6 months before study
entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers,
calcium channel blockers, and digoxin are permitted).
- Clinically relevant findings in the ECG such as a second- or third-degree
atrioventricular block, prolongation of the QRS complex ≥ 120 ms, or prolongation
of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise
between the investigator and the sponsor's medically responsible person. QTc >
450 ms detected in 2 or more time points within a 24-hour period are excluded.
- Clinically significant arterial hypertension despite optimal medical management
(per investigator´s opinion). Clinically significant hypertension defined as
systolic blood pressure above 150 mmHg and/or diastolic blood pressure above 90
mmHg, despite optimal medical management. For participants taking
antihypertensive medication, blood pressure should be stable/ controlled for more
than 7 days before first dose of study medication.
- Previous treatment with an ATR Inhibitor
- Participants in Part A and Part B (Sub-population 2): Previous treatment with known or
putative PARPi, if discontinued for CTCAE grade ≥ 3 AEs or CTCAE grade ≥ 3
hypersensitivity to PARPi. Participants in Part B Sub-population 1 must not have
received prior PARPi treatment.
Protocol #: 19-810