Ovarian Granulosa Cell Tumor MedDRA version: 27.0 Level: PT Classification code 10073260 Term: Ovarian granulosa cell tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: LLT Classification code 10073273 Term: Ovarian granulosa cell tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: nirogacestat
Product Code: PF-03084014
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Nirogacestat
CAS Number: 1962925-29-6
Current Sponsor code: PF-03084014
Other descript
Sponsors
SpringWorks Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be aged = 18 years of age inclusive 2. Participant has histologically confirmed recurrent adult-type granulosa cell tumor of the ovary prior to first dose of study treatment and agrees to provide archival or fresh tumor tissue. 3. Participant must have documented radiological evidence of relapse after at least one systemic therapy that is not amenable to surgery, or radiation and have measurable disease by RECIST v1.1 criteria. Prior systemic therapy is not limited to therapy type nor is any specific prior line of therapy required. 4. Participant must have a ECOG performance Grade of 0, 1, or 2 at Screening. 5. Participant must have adequate bone marrow, renal and hepatic function as defined by the following Screening laboratory values: a. Absolute neutrophil count (ANC) =1,000 cells/µL; b. Platelets = 75,000/µL; c. Estimated glomerular filtration rate (eGFR) = 60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Grade = 1). d. Total bilirubin = 1.5 ×ULN (isolated total bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Participant has any of the following: • Signs of bowel obstruction who require parenteral nutrition. • Malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat (e.g., gastric bypass, lap band, or other gastric procedures that would alter absorption). 2.Participant has experienced any of the following within 6 months of signing informed consent: • Clinically significant cardiac disease (New York Heart Association Class III or IV); • Myocardial infarction; • Severe/unstable angina; • Coronary/peripheral artery bypass graft; • Symptomatic congestive heart failure; • Cerebrovascular accident; • Transient ischemic attack; or • Symptomatic pulmonary embolism. 3. Participant has abnormal QT interval corrected by Fridericia’s formula (> 470 msec for female participants, or > 480 msec for participants with bundle branch block) after electrolytes have been corrected at Screening. 4. Participant has congenital or acquired long QT syndrome or a history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 5. Participant has current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones). 6. Participant has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment. 7. Participant has a history of other invasive malignancies, with the exception of nonmelanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years. Participants are also excluded if their previous cancer treatment contraindicates this protocol therapy. 8. Participant has CTCAE v5.0 Grade > 1 toxicity from prior therapy (except alopecia, anorexia or CTCAE grade 2 peripheral neuropathy). 9. Palliative radiotherapy with a limited field of radiation within 14 days or with wide field of radiation or to more than 30% of bone marrow within 28 days prior to the first dose of study treatment. 10. Participant previously received or is currently receiving therapy with GS inhibitors (i.e., nirogacestat) or anti-Notch antibody therapy. 11. Previous or current treatment for OvGCT: a. Participant previously received or is currently receiving bevacizumab (or other monoclonal antibody therapy with targeted anti-angiogenic activity) for OvGCT within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment; or b. Participant has received the following treatment types for OvGCT within 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment: • hormonal therapy; • chemotherapy; • immunotherapy; • targeted therapy (e.g., tyrosine kinase inhibitors [TKIs], small molecule inhibitors); or • any other investigational treatment. 12. Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 3A4 (CYP3A4) inhibitors, or strong CYP3A inducers within 14 days prior to the first dose of study treatment. 13. Participant is using concomitant medications that are known to prolong the QT/QTcF interval including Class Ia (e.g., quinidine, procainamide, disopromide) and Class III (e.g., dofetilide, ibutilide, sotalol) antiarrhythmics at the time of informed consent. Non-antiarrhythmic medications which may prolong the QT/QTcF interval are allowed provided the partici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the anti-tumor activity of nirogacestat in adult participants with relapsed/refractory OvGCT;Secondary Objective: - To determine if nirogacestat delays progression or death in OvGC - To describe overall survival in participants treated with nirogacestat - To determine the effect of nirogacestat on ovarian cancer symptoms measured by Functional Assessment of Cancer Therapy – Ovarian Symptom Index (FOSI) - To determine the duration of response - To determine the pharmacokinetics (PK) of nirogacestat;Primary end point(s): Objective response rate, defined as the proportion of participants with Complete Response (CR) + Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;Timepoint(s) of evaluation of this end point: There is not any defined timepoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Estimate of proportion of participants who have not progressed or died at 6 months follow-up: PFS-6. Progression is defined by RECIST v1.1 - Estimate of 2-year overall survival, defined as the proportion of participants who have not died after 2 years of follow-up after their first dose of nirogacestat - Change from baseline in FOSI - Duration of response, (DoR), defined as the time from first assessment of response (CR + PR using RECIST v1.1) to first disease progression defined by RECIST v1.1 or death, whichever comes first - Serum concentrations of nirogacestat will be measured to evaluate system exposures (Cmax, Ctrough and other PK parameters as data allow);Timepoint(s) of evaluation of this end point: There is not any defined timepoint. | — |
Countries
Canada, France, Poland, Spain, United States
Contacts
Public ContactResearch and Development - CO dpt.
SpringWorks Therapeutics, Inc.
Outcome results
None listed