GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer

• Have a histologically confirmed diagnosis of advanced (unresectable, recurrent, and/or metastatic) endometrial carcinoma that is incurable and for which prior standard first-line treatment has failed.
• Prior to Cycle 1 Day 1 (C1D1), documentation of tumor dMMR/MSI-H status must be available based on local testing.
• Must have progressed on or after at least 1 (but no more than 2) prior line(s) of a systemic chemotherapy regimen for unresectable and/or metastatic endometrial cancer of which at least 1 regimen of platinum-based treatment unless participant is ineligible for or intolerant to platinum.
• Cohort A only: Must be treatment naive for CPIs including PD-1 or PD-L1 inhibitors and other immune CPIs (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT).
• Cohort B only: Must have received and progressed on or after prior treatment with a PD-1/PD-L1 inhibitor alone or in combination. Moreover, the participant's duration of CPI containing treatment and best overall response (BOR) is known, and participant has received a minimum of 2 cycles of CPI.

Exclusion Criteria:

• Histological diagnosis of carcinosarcoma, malignant mixed Műllerian tumor, endometrial leiomyosarcoma, or endometrial stromal sarcomas.
• Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
• Any prior treatment with any type of antitumor vaccine, or autologous cell immunotherapy.
• Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
• Treatment with an anticancer agent, including investigational vaccines within 28 days before or 5 times t1/2, whichever is shorter, prior to the planned first dose of trial treatment or is currently enrolled in an interventional trial.
• Prior treatment with live, attenuated vaccines within 30 days prior to initiation of trial treatment.
• Received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support within 4 weeks before the planned first dose of trial treatment.
• Cohort A only: Prior exposure to immune CPIs other than anti-PD-1/anti-PD-L1 (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40)

• Cohort B only:

  • Known history of Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy treatment
  • Exposure to any of the following prior therapies/treatments within the specified timeframes:
  • Prior exposure to immune CPIs other than anti-PD-1/anti-PD-L1 (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40)
  • PD-1/PD-L1 antibody within 28 days before the planned first dose of trial treatment

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.