Symbiotic-GYN-18: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Advanced or Recurrent MMR-proficient Endometrial Cancer

This study is being conducted to assess whether the study medicine PF 08634404, given in combination with chemotherapy, improves outcomes compared with another medicine called pembrolizumab plus chemotherapy. Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. Our bodies have a built-in DNA "spell-checker," called the mismatch repair (MMR) system, that fixes genetic mistakes. In most endometrial cancers, this system works normally, and these cancers are called MMR-proficient (pMMR). However, pMMR tumors are harder for the immune system to recognize and attack. When endometrial cancer has spread beyond the uterus or comes back after previous treatment, it is called advanced or recurrent endometrial cancer. This study is for adults with mismatch repair-pMMR advanced or recurrent endometrial cancer. Participants must meet key criteria, including: * Women who are 18 years or older, and not pregnant at the time of joining the study * pMMR endometrial cancer only * Measurable Stage III disease, Stage IV disease (with or without measurable disease) per FIGO staging, a system doctors use to describe how far cancer has spread in the body, or recurrent (with or without measurable disease) endometrial cancer * Has not received chemotherapy except for chemotherapy given after the main surgery and more than 6 months before relapse * Be in good enough health to receive study treatment. Approximately 600 adult women will be enrolled. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups, with about half in each group. The study is open, meaning both the doctors and participants know what treatment is being given. Participants will receive their assigned treatment through intravenous infusions (medicine is given directly into a vein). The treatment will be given in cycles. Experimental Group will receive new study medicine called PF-08634404 plus chemotherapy. It will be followed by PF 08634404 alone for up to 2 years (35 cycles). Control Group will receive an approved medicine called pembrolizumab plus chemotherapy. It will be followed by pembrolizumab alone for up to 2 years (20 cycles). The study will include regular visits for: * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will come for a final visit within a month to check their health and review any reactions. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records. This helps check health and any new treatments. * Tests will be done every 9 weeks during the first 104 weeks to see how the cancer is responding. After that, tests will be done every 12 weeks.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Women ≥18 years of age who are confirmed not pregnant at screening.
* Histologically or cytologically confirmed endometrial cancer that is recurrent or advanced; carcinosarcomas are eligible but pure sarcomas are excluded.
* Newly diagnosed FIGO Stage III disease with measurable disease per RECIST v1.1, newly diagnosed FIGO Stage IV disease with or without measurable disease, or recurrent disease with or without measurable disease for which curative treatment with surgery and/or radiotherapy is unlikely.
* For participants with recurrent disease, prior adjuvant systemic anti-cancer therapy is allowed if relapse occurred more than 6 months after the last dose.
* Must provide tumor tissue for prospective central assessment of MMR and p53 status.
* Proficient mismatch repair (pMMR) endometrial cancer as determined by central testing.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Life expectancy of at least 12 weeks.
* Adequate organ function as defined in the protocol.

Exclusion Criteria:

* Prior systemic therapy for first-line advanced or recurrent endometrial cancer.
* Prior immunotherapy or anti-angiogenic therapy.
* Deficient mismatch repair (dMMR) endometrial cancer by central testing.
* Active or untreated central nervous system (CNS) metastases; participants with previously treated and clinically stable brain metastases may be eligible if not requiring steroids and without evidence of progression.
* Clinically significant risk of bleeding or fistula, including a history of severe bleeding disorders.
* History of another malignancy within 3 years, except for cancers with negligible risk of recurrence or death.
* History of allogeneic organ or hematopoietic stem cell transplantation; active autoimmune disease requiring systemic treatment within the past 2 years; or history of immunodeficiency
* Interstitial lung disease, pneumonitis, or clinically significant pulmonary disease
* Uncontrolled or significant cardiovascular, metabolic, renal, hepatic, or vascular disease
* Active or uncontrolled infection.
* Recent major surgery or severe trauma within protocol-defined washout periods.