GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies

Key Inclusion Criteria:

* Participant must have a histologically-confirmed non-central nervous system (CNS) solid tumor that is metastatic or unresectable and for whom there is no available standard therapy likely to confer clinical benefit; or a participant who is not a candidate for such available therapy and for whom, in the opinion of the investigator, experimental therapy with acasunlimab or acasunlimab in combination with pembrolizumab may be beneficial.
* Asian race and Japanese ethnicity.
* Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Have Eastern Cooperative Oncology Group (ECOG) 0-1.
* Have an acceptable hematological status.
* Have acceptable liver function.
* Have an acceptable coagulation status.
* Have acceptable renal function.
* Should provide a tumor tissue sample (formalin-fixed paraffin-embedded \[FFPE\] blocks/slides) from archival tissue or fresh biopsy collected before C1D1, preferably derived from advanced disease stage.

Key Exclusion Criteria:

* Have uncontrolled intercurrent illness, including but not limited to:

  * 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.
  * Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
  * Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.
  * Ongoing or recent evidence of autoimmune disease.
  * History of irAEs that led to prior checkpoint treatment discontinuation.
  * Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
  * History of chronic liver disease or evidence of hepatic cirrhosis.
  * Evidence of interstitial lung disease.
  * History of non-infectious pneumonitis that has required steroids or currently has pneumonitis.
  * History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of trial treatment.
  * Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
* Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke.
* Prior therapy:

  * Radiotherapy: Radiotherapy within 14 days prior to the first dose of trial treatment. Palliative radiotherapy will be allowed.
  * Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to trial treatment administration.
* Toxicities from previous anti-cancer therapies that have not adequately resolved.

Note: Other protocol specified inclusion/exclusion criteria may apply.