Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy

Inclusion Criteria:

All cohorts:

* Be at least 18 years of age.
* Have measurable disease according to RECIST v1.1.
* Provide all pre-baseline scans since failure of last prior therapy (ie, documented radiographic progressive disease \[PD\]), if available.
* Have Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1 at screening and on C1D1 pretreatment.
* Provide a biopsy (ie, formalin-fixed paraffin-embedded slides/block). A fresh biopsy taken during the screening period is preferred, unless medically unfeasible and after review and approval by the sponsor. If this cannot be provided, a biopsy taken after failure/stop of last prior treatment and taken within 6 months prior to C1D1 may be provided.

Phase 1a and 1b- Dose Escalation:

* Have histologically or cytologically confirmed non-Central Nervous System (CNS) primary solid tumors who have metastatic or advanced disease.
* Have progressed on standard of care (SoC) therapy which should include platinum-based chemotherapy and anti-PD/PD-L1 therapies, if applicable for the tumor type, or for whom there is no available standard therapy likely to provide clinical benefit, and for whom experimental therapy with GEN1055 or GEN1055+pembrolizumab may be beneficial, in the opinion of the investigator.

Phase 2a - Expansion:

Inclusion criteria specific to selected tumor indications may apply.

Exclusion Criteria:

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

  * Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose (including coronavirus disease 2019 \[COVID-19\] infection).
  * Significant cardiovascular impairment including:

    i) Symptomatic congestive heart failure (Class III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia.

ii) Uncontrolled hypertension defined as systolic blood pressure ≥160-millimeter (mm) Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.

iii) Prolonged corrected QT interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula.

* Ongoing or recent (within 1 year of screening) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs).
* History of grade 3 or higher irAEs that led to treatment discontinuation of a checkpoint inhibitor (CPI). A participant with irAEs below grade 3 that led to discontinuation should be discussed with the sponsor. Grade 3 irAEs that have fully recovered may also be discussed.
* History of chronic liver disease (eg, alcoholic hepatitis or nonalcoholic steatohepatitis), drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis.
* Evidence of interstitial lung disease.
* Ongoing pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of noninfectious drug-, immune-, or radiation-related pneumonitis that has required steroids.

  * Has been exposed to any of the following prior therapies/treatments within the specified timeframes:
* Treatment with an anticancer agent within 4 weeks or for systemic therapies within 5 half-lives of the drug, whichever is shorter, prior to trial treatment administration.
* Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Has received granulocyte or granulocyte/macrophage colony-stimulating factor support within 2 weeks prior to first trial treatment administration or is chronically transfusion-dependent.
* RT within 14 days before the planned first dose of trial treatment. Palliative RT of bone metastases up to 7 days prior to C1D1 will be allowed.

  * Hepatitis (testing for hepatitis B or C is not required unless mandated by local health authority):
* Hepatitis B virus (HBV): Has a medical history or positive serology for HBV (defined as positive for hepatitis B surface antigen or HBV deoxyribonucleic acid \[DNA\]).

  i) Above is not exclusionary if deemed due to vaccination, resolved natural infection, or passive immunization due to immunoglobulin therapy.
* Hepatitis C virus (HCV): Known active HCV infection (defined as positive for HCV ribonucleic acid \[RNA\] \[qualitative\]).

Note: Other protocol defined inclusion and exclusion criteria may apply.