The sponsor has made the decision to terminate further development of GEN1078 based on emerging safety observations and overall benefit-risk assessment of 1078

The purpose of this trial is to measure the following in participants with solid cancers who receive GEN1078.

• The side effects seen with GEN1078
• What the body does with GEN1078 once it is administered
• What GEN1078 does to the body once it is administered
• How well GEN1078 works against advanced solid tumors

Trial details include:

• The estimated trial duration is 8 months for an individual participant (the trial duration may vary for each participant).
• The treatment duration will be an estimated 3-month treatment period (the duration of treatment may vary for each participant).
• The visit frequency will be daily or visits every few days for the first few months.

All participants will receive active drug; no one will be given placebo.

Key Inclusion Criteria:

• Must have at least 1 measurable lesion per RECIST v1.1 assessed by the investigator.
• Must have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1.

Dose Escalation Only

• Participant must have histologically or cytologically confirmed solid tumor(s) for which there is no further available standard therapy likely to confer clinical benefit (or participant is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1078 may be beneficial.
• Must have either recurrence after, or progression on available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting.

Expansion Only

• Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis of selected solid cancers.

Key Exclusion Criteria:

• Has significant cardiovascular impairment within 6 months prior to the first dose of trial drug, including presence of unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] class III and IV), or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.

• Known unstable central nervous system (CNS) metastases or any active or history of carcinomatous meningitis.

• Has been exposed to any of the following prior therapies within the specified timeframes:

  • Prior therapy with a compound targeting the same targets as GEN1078 or any cell-based therapies.
  • Radiotherapy within 14 days prior to C1D1. Palliative radiotherapy of bone metastases up to 7 days prior to C1D1 will be allowed.
  • Treatment with any investigational or non-investigational anticancer agent (including investigational vaccines) or used an invasive investigational medical device within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first dose of GEN1078.
  • Chemotherapy within 2 weeks prior to the first dose of GEN1078.
  • Prophylaxis with live, attenuated vaccines within 28 days prior to first dose of GEN1078; or prophylaxis with the first and/or subsequent injection(s) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid vaccine within 14 days prior to first dose of GEN1078.
  • Chronic systemic immunosuppressive treatment, including corticosteroids, ie, prednisone >10 milligrams (mg) daily (or equivalent) or a cumulative dose >140 mg prednisone within 14 days (or equivalent) before the first dose of GEN1078. Replacement therapy (eg, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
  • Has received granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within 2 weeks prior to the first dose GEN1078 or being chronically transfusion dependent.
  • Has received other T-cell activating surface marker. Note: Prior treatment with anti-T-cell Ig and ITIM domain (aTIGIT), anti-programmed cell death protein 1 (aPD1), anti-programmed death-ligand 1 (aPDL1), anti-lymphocyte activation gene 3 protein (aLAG3), anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) is allowed.
  • The initiation of growth factors and bisphosphonates is not allowed during the first 4 weeks of GEN1078 administration, unless agreed upon by the investigator and sponsor medical monitor. However, the use of receptor activator of nuclear factor kappa-Β ligand (RANK-L) inhibitors and bisphosphonates (if on stable dose for at least 4 weeks) is permitted while participating in this trial.

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