A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors

A Phase II, Open-Label, Multicenter, Platform Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors

This study will evaluate the efficacy and safety of multiple biomarker-selected treatments in patients with persistent or recurrent rare epithelial ovarian, fallopian tube, or primary peritoneal tumors. Enrollment will take place in two phases: a preliminary phase followed by a potential expansion phase.

Inclusion Criteria:

• Persistent or recurrent EOC that meets the following criteria: Histologically confirmed non-high-grade serous, non-high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, including but not limited to low-grade serous ovarian carcinoma, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, seromucinous carcinoma, malignant Brenner tumors, Grades 1 or 2 endometrioid carcinoma, mesonephric-like adenocarcinoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Disease that is not amenable to curative surgery
• Measurable disease (at least one target lesion) according to RECIST v1.1
• Previous treatment with one to four lines of therapy, at least one of which was platinum-based. Hormonal therapy does not count as a line of therapy.
• Platinum-resistant disease, defined as disease progression during or within 6 months of last platinum therapy, with the following exception: Participants with primary platinum-refractory disease are excluded.
• Submission of a representative tumor specimen that is suitable for next-generation sequencing (NGS) testing and estrogen receptor immunohistochemistry (ER IHC) to determine treatment arm assignment and for central pathology review.
• Submission of the local pathology report and, if available, any associated stained slides that supported the local diagnosis of the histology (to be used for central pathology review)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs (if applicable)
• In addition to the general inclusion criteria above, participants must meet all of the arm-specific inclusion criteria for the respective arm

General Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant or breastfeed during the study
• Primary platinum-refractory disease, defined as progression during or within 4 weeks after the last dose of the first-line platinum treatment
• Histologic diagnosis of high-grade serous or high-grade endometrioid ovarian, fallopian tube, or primary peritoneal cancer
• Current diagnosis of solely borderline epithelial ovarian tumor
• Current diagnosis of non-epithelial ovarian tumors
• Current diagnosis of synchronous primary endometrial cancer
• Prior history of primary endometrial cancer, with the following exception: a prior diagnosis of primary endometrial cancer is permitted if it meets all of the following conditions: Stage IA, no lymphovascular invasion, International Federation of Gynecology and Obstetrics Grade 1 or 2, not a high-grade subtype.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Symptomatic, untreated, or actively progressing CNS metastases
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with chemotherapy, radiotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or investigational therapy within 28 days prior to initiation of study treatment
• Treatment with hormonal therapy within 14 days prior to initiation of study treatment
• In addition to the general exclusion criteria above, participants can not meet any of the arm-specific exclusion criteria for the respective arm