A clinical study of the anti-cancer effects of an investigational therapy or chemotherapy in patients with recurring uterine cancer

Prior treatment

• Are ineligible for all options in the investigator’s choice chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).
• Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates (ADCs).
• Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of trial treatment.
• Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, or peritoneal shunt within 2 weeks prior to the first dose of trial treatment.
• Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of trial treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.
• Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement, and/or prior pneumonectomy (complete).
• Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of trial treatment.
• Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia, fatigue, or endocrinopathies that are well controlled) not yet resolved to Grade 1 or below, or baseline.

Other illness

• Have a history of allergies, hypersensitivities, or intolerance to trial treatments including any excipients thereof or to other monoclonal antibodies. Participants who have successfully undergone a desensitization process and are able to tolerate the drug are eligible.
• Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
• Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

Lab values

• Have left ventricular ejection fraction (LVEF) below 55% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to the first dose of trial treatment.

Other

• Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.

• Are female adults.
• Have histologically confirmed endometrial cancer that: − is recurrent, − has a HER2 IHC score of 1+, 2+ (Cohort 1), or 3+ (Cohort 2) as determined by central laboratory testing for HER2 expression, and − is not defined as a true sarcoma.
• Have measurable disease defined by RECIST 1.1.
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Have recurrent endometrial cancer and meet any of the following: -developed recurrence within less than 12 months from completing platinum-based chemotherapy as adjuvant therapy for Stage I to III disease, or -developed recurrence after platinum-based chemotherapy in the recurrent / metastatic setting.
• Have a life expectancy of 12 weeks or longer at screening.
• Have received prior immune-checkpoint inhibitor (ICI) treatment (i.e., anti-PD-1/anti-PD-L1).
• Up to three lines of prior therapy are allowed.