Gynecologic

Title: A Phase 3, Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab With or Without Bevacizumab Compared With Standard of Care as Firstline Maintenance Treatment for Participants With Persistent, Recurrent, or Newly Diagnosed Metastatic Cervical Cancer With PD-L1 CPS Greater Than or Equal to 1 (TroFuse-036/GOG-3123/ENGOT-cx22)

MOA: Sacituzumab tirumotecan (Sac-TMT) is a TROP2-targeted ADC with a topoisomerase I inhibitor payload.

Key Eligibility:

Part 2 induction: Screening

• Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma or
  adenocarcinoma of cervix
• Persistent/recurrent/newly diagnosed metastatic cervical cancer not amenable to
  curative tx
• PD-L1 CPS ≥1 per the central laboratory
• Measurable disease per RECIST 1.1
  before induction
• Prior tx with anti-PD-(L)1/2 or another stimulatory/coinhibitory T-cell receptor, anti
  TROP2 ADC, bispecific agents targeting PD-(L)1, any ADC for cervical cancer, or
  systemic anticancer tx excluded
  • Prior CRT or induction chemo prior to RT in LACC setting is allowed
    
• Part 2: Maintenance and Optional Subsequent Treatment
• Valid TROP2 result per the central laboratory before randomization
• Maintenance only:
  • Has completed 6 cycles of induction before randomization and achieved CR, PR, or
    SD per RECIST v1.1 by investigator
• Optional Subsequent Treatment:
  • BICR-verified PD per RECIST 1.1 during/after protocol-specified induction but before
    randomization to Maintenance

Phase 3, Randomized, Open-label, Multicenter Study of Sacituzumab Tirumotecan Maintenance With or Without Bevacizumab vs Standard of Care in Participants With Newly Diagnosed Advanced HRD Negative Ovarian Cancer Following First-line Platinum-based Chemotherapy (TroFuse-021/ENGOT-ov85/GOG-3102)

MOA: Sacituzumabtirumotecan (Sac-TMT) is a TROP2 targeting ADC with a TOP1i payload.

Key Eligibility

• Confirmed FIGO Stage III or IV epithelial OC/FT/PPC
  • Allows high-grade serous, endometrioid, carcinosarcoma/mixed
    Müllerian with high-grade serous component, clear cell, low-grade
    serous histologies
• Has undergone debulking surgery (primary [PDS] or interval [IDS])
• Must have completed 4-6 cycles of 1L plt-based chemo
  • For IDS: ≥2 but preferably 3 cycles of 1L plt-based chemo after
    surgery
• ≤12 weeks between last dose of 1L plt-based chemo and randomization
• Has CR, PR, SD, or NED by the investigator to 1L plt-based chemo at
  screening (based on RECIST 1.1 and CA-125 levels and evaluated
  between 3-6 weeks after last dose of plt)
• Not eligible to receive PARPi as 1L maintenance tx
• HRD-negative and known TROP2 status by prospective central testing
• Prior tx with TROP2-targeted ADC or topoisomerase I-containing ADCs
  are excluded

A Prospective Low-interventional Phase 4 Single Arm Study Of Ocular Assessments In Patients Treated With Tivdak® In Recurrent Or Metastatic Cervical Cancer

MOA: Tisotumab vedotin-tftv (Tivdak®) is a tissue factor (TF)-directed ADC with an MMAE payload.

Key Eligibility:

• Recurrent/metastatic cervical cancer with PD on/after
  chemotherapy
• Tivdak recommended by physician according to US prescribing
  information
• Must be willing to undergo repeated ocular assessments
• Pts with active ocular disease at baseline are excluded
• Previous treatment with Tivdak is excluded
• Prior tx with an investigational drug within 30 days is excluded
• Pts are advised to avoid wearing contact lenses for the entire
  duration of therapy

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)

ISD Substudy Additional Exclusion Criteria

• Diabetes mellitus requiring insulin
• BMI <20 kg/m2
• History of severe constipation
• History of anaphylaxis from food allergy or other disease
  state requiring avoidance of a particular food
• Diagnosed eating disorder in last 10 years
• Condition where high-fat diet would be contraindicated
• History of severe hyperuricemia or gout
• Pts w/ history of severe nephrolithiasis must be approved
  by medical monitor
• Pts on SGLT-2 inhibitors may be allowed after discussion
  with medical monitor

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 is a small molecular inhibitor of the WEE1 tyrosine kinase.

Key Eligibility Criteria:

• Histologically or cytologically diagnosed high-grade serous OC/FP/PPC FFPE tumor tissue must be submitted for prescreening – only positive cyclin E1 protein status (IHC) is eligible
• Must have plt-resistant disease
  • Primary plt-refractory excluded
• Prior bevacizumab required if eligible
• Prior PARPi as maintenance required if BRCA1/2m or HRD
• Prior MIRV required if indicated
• Measurable disease per RECIST v1.1
• Prior tx with WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, PKMYT1
  inhibitor or CDK2 inhibitor are excluded
• Part 2b: 1-3 prior lines of systemic tx
  • Up to 4 prior lines of tx allowed if pt received MIRV
• Part 2c: 1-4 prior lines of tx AND
  • Weekly taxane regimen as monotherapy or in combination with
    another agent(s) in the PROC setting. Nab-paclitaxel is allowed