This study is testing a new medicine called PF-08634404 and how it works in adults with advanced Renal Cell Carcinoma (RCC)- a type of kidney cancer that is either locally advanced (spread to nearby tissues) or metastatic (spread to other parts of the body). The study will look at the safety of the study medicine, when given alone or with other anticancer medicines, and how this type of cancer responds to them.

To join the study, participants must be adults; with locally advanced or metastatic RCC; who have not received treatment for their advanced kidney cancer.

Participants will receive study medicine either alone or with other anticancer medicines. The medicine will be given through intravenous (IV) infusions, which means it will be injected directly into a vein. All treatments will take place at clinical study sites, where trained medical staff will take care of participants during and after each visit.

Inclusion Criteria:

• 18 years of age or older at screening
• Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC with diagnosis confirmed by histology/cytology
• At least one measurable (as defined by the investigator) and untreated lesion
• Adequate hematologic, hepatic, cardiac and renal function
• No prior systemic therapy for RCC (immunotherapy after surgery is allowed if received >12 months prior)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• All International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) based risk categories

Exclusion Criteria:

Participants may be excluded if they meet any of the following:

• Known active brain lesions including leptomeningeal metastasis, brainstem, meningeal or spinal cord metastases or compression.
• Clinically significant risk of haemorrhage or fistula
• History of another malignancy within 3 years
• History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• active autoimmune diseases requiring systemic treatment within the past 2 years
• uncontrolled cardiac and other comorbidities within 6 months prior to the first dose
• Major surgery or severe trauma within 4 weeks before the first dose, or planned major surgery during the study
• History of severe bleeding tendency or coagulation dysfunction
• History of oesophageal varices, severe ulcers, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months prior to the first dose
• Acute, chronic or symptomatic infections
• Participants with history of immunodeficiency

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.