Gynecologic

An Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) with Paclitaxel, and a Substudy Evaluating PIKTOR with Paclitaxel plus an Insulin-Suppressing Diet, in Patients with Advanced or Recurrent Endometrial Cancer (FTH-PIK-201)

MOA: PIKTOR is a combination of sapanisertib, an mTORC1 and 2 inhibitor, and serabelisib, a PI3Kα inhibitor.

Key Eligibility Criteria:

• Histologically confirmed advanced/recurrent endometrioid
  endometrial carcinoma
• 1-4 prior systemic therapies, including plt-based chemo and an
  immune checkpoint inhibitor, separately or in combo
• PI3K/AKT/mTOR pathway gene alteration required as identified
  by historical tumor testing within the previous 5 years
• At least 1 measurable target lesion per RECIST v1.1
• Prior PI3Ki, AKTi, dual mTORC1/2i, or dual PI3K/mTORi
  excluded
• Prior mTORC1 inhibitor allowed (e.g., everolimus, temsirolimus)
• Optional insulin-suppressing diet substudy (see Page 2 for
  additional exclusion criteria)

A Phase 2 Study Evaluating The Efficacy And Safety Of TORL-1-23 In Women With Advanced Platinum Resistant Epithelial Ovarian Cancer (Including Primary Peritoneal And Fallopian Tube Cancers) Expressing Claudin 6 (CLND6) (TORL123-002)

MOA: TORL-1-23 is an ADC that targets CLDN6 and contains a MMAE payload.

Key Eligibility Criteria:

• Histologically or cytologically confirmed diagnosis of advanced (unresectable) or metastatic high grade serous OC/PP/FPC
• High-grade endometrioid permitted
• Clear cell, mucinous, sarcomatous (incl carcinosarcoma), mixed histology, low grade, borderline ovarian tumors, non-epithelial ovarian cancers excluded
• Pt must have platinum-resistant disease
• Primary plt-refractory excluded
• 1-3 prior systemic lines of therapy, eligible for single-agent as next tx
• Prior bevacizumab for treatment of OC per label required unless ineligible
• Prior MIRV required for FOLR1-high (FRα ≥ 75%) disease unless ineligible
• Prior PARPi maintenance required for pts with BRCA mutation unless ineligible
• Prior tx with CLDN6-targeting agent or MMAE-containing ADC excluded
• Tumor must be CLDN6+ (>30% tumor cell membrane staining of any intensity by IHC)
• Measurable disease per RECIST v1.1

A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Subjects with High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

MOA: Azenosertib inhibits WEE1, accelerating the cell cycle and driving cancer cells with genetic instability or replication stress into apoptosis

Key Eligibility Criteria:

• Histologically or cytologically diagnosed high-grade serous OC/FP/PPC
• Must have plt-resistant disease
• Primary plt-refractory excluded
• 1-3 prior lines of therapy
• Prior bevacizumab required if eligible
• Prior PARPi as maintenance required if BRCA1/2m or HRD
• Prior MIRV required if indicated
• Up to 4 prior lines of tx allowed if pt received MIRV
• Part 2 requires positive cyclin E1 protein status result determined by IHC
• Measurable disease per RECIST v1.1
• Prior therapy with any WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor or PKMYT1 inhibitor excluded

A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women with Recurrent or Persistent Uterine Serous Carcinoma (ZN-c3-004 | GOG 3065)

MOA: ZN-c3 is a novel, selective and orally bioavailable small-molecular inhibitor of the WEE1 tyrosine kinase.

Key Eligibility:

• Histologically confirmed recurrent/persistent USC for which no other proven effective treatment options are available or any available SOC therapy was not tolerated or was refused by the subject
• Endometrial carcinoma of mixed histology with the serous component ≥10% of the tumor will be considered eligible
• Measurable disease per RECIST v1.1
• ECOG PS of ≤1
• Treatment with ≥1 prior platinum-based chemotherapy regimen for management of advanced/metastatic USC
• Major surgery <28 days; any chemotherapy <14 days/5 half-lives; radiation therapy <21 days (eligible if the radiation portal covered ≤5% of the bone marrow); autologous/allogeneic SCT <3 months excluded
• Prior treatment with a cell cycle checkpoint inhibitor/ZN-c3/any other WEE1 inhibitor excluded
• Brain metastases that require immediate treatment or are clinically/radiologically unstable
• Second malignancies/requiring therapy