Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Chemotherapy + avelumab followed by avelumab + talazoparib; Chemotherapy followed by talazoparib maintenance; Chemotherapy + bevacizumab followed by bevacizumab
Intervention description: Chemotherapy Period Paclitaxel Carboplatin Avelumab
Maintenance Period Avelumab Talazoparib; Chemotherapy Period Paclitaxel Carboplatin
Maintenance Period Talazoparib; Chemotherapy Period Paclitaxel Carboplatin Bevacizumab
Maintenance Period Bevacizumab
Intervention MeSH terms: Bevacizumab; Avelumab; Talazoparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 79.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: untreated epithelial ovarian cancer; fallopian tube cancer; primary peritoneal cancer

Summary:

      JAVELIN Ovarian PARP 100 (B9991030) is an open-label, randomized study designed to evaluate
      the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance
      therapy of avelumab in combination with talazoparib versus an active comparator in
      treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or
      Stage IV). On March 19, 2019, Sponsors alliance announced the discontinuation of the ongoing
      Phase III study, and the decision was based on several factors, including previous announced
      interim results from JAVELIN Ovarian 100 study (B9991010). Patients who remain in B9991030
      study will continue receiving their randomized treatment assigned and will be monitored for
      appropriate safety assessments until treatment discontinuation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed Stage III IV epithelial ovarian, fallopian tube, or primary
             peritoneal cancer including carcinosarcoma with high-grade serous component.

          -  Patients must be candidates for bevacizumab in combination with platinum based
             chemotherapy and previously untreated.

          -  Must have completed a primary surgical debulking procedure, or be candidates for
             neoadjuvant chemotherapy with planned interval debulking surgery.

               1. Patients who completed primary debulking must have had incompletely resected
                  disease that is macroscopically/grossly visible and at least with lesions >1 mm
                  and be randomized at a maximum of 8 weeks after surgery.

               2. For patients who are candidates for neoadjuvant chemotherapy, the diagnoses must
                  have been confirmed by:

                    -  Core tissue (not fine-needle aspiration) biopsy is required for diagnosis.

                    -  Stage IIIC-IV documented via imaging or surgery (without attempt at
                       cytoreduction).

                    -  Serum CA-125/CEA ratio >25. If the serum CA-125/CEA ratio is <25, then
                       workup should be negative for the presence of a primary gastrointestinal or
                       breast malignancy (<6 weeks before start of neoadjuvant treatment).

                    -  Randomization must occur within 8 weeks after diagnosis.

          -  Availability of an archival FFPE tumor tissue block or a minimum of 25 slides,
             together with an accompanying original H&E slide. If archived FFPE tissue is not
             available, a de novo (ie, fresh) tumor sample must be obtained in accordance with
             local institutional practice for tumor biopsies. Tumor tissue must contain 40% or
             greater tumor nuclei per central laboratory assessment.

          -  ECOG performance status 0-1

          -  Age >=18 years (or >=20 years in Japan).

          -  Adequate bone marrow, hepatic, and renal function and blood coagulation

        Exclusion Criteria:

          -  Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline
             tumors) or mucinous tumors.

          -  Patients for whom intraperitoneal cytotoxic chemotherapy is planned.

          -  Prior exposure to immunotherapy with interleukin (IL)-2, interferon alpha (IFN-α), or
             an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte
             associated antigen 4 (anti-CTLA4) antibody (including ipilimumab), or any other
             antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint
             pathways, excluding therapeutic anticancer vaccines.

          -  Prior treatment with a PARP inhibitor.

          -  Prior treatment with any anti-vascular endothelial growth factor (VEGF) drug,
             including bevacizumab.

          -  Major surgery (other than debulking or exploratory surgery for ovarian cancer) for any
             reason within 4 weeks prior to randomization and/or incomplete recovery from surgery.

          -  Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior radiation
             for localized cancer of the breast, head and neck, or skin is permitted, provided that
             it was completed more than three years prior to registration, and the patient remains
             free of recurrent or metastatic disease.

          -  Prior targeted therapy (including but not limited to vaccines, antibodies, tyrosine
             kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal
             primary or fallopian tube carcinoma.

          -  Prior organ transplantation including allogenic stem cell transplantation.

          -  Diagnosis of Myelodysplastic Syndrome (MDS).

          -  Known symptomatic brain metastases requiring steroids. Patients with previously
             diagnosed brain metastases are eligible if they have completed their treatment and
             have recovered from the acute effects of radiation therapy or surgery prior to study
             enrollment, have discontinued corticosteroid treatment for these metastases for at
             least 4 weeks and are neurologically stable.