The purpose of this trial is to learn about the safety and efficacy of GEN1119 when it is used for the treatment of participants with certain types of cancer.

The trial has multiple parts. The first part of the trial will test different doses of GEN1119 to find out if it is safe and to determine what are the best doses to use. The second part will further refine this optimal dose. The third part continues to test the safety and how well GEN1119 works in additional participants with specific cancer types and at doses chosen based on the results of the first 2 parts of the trial.

For each participant, the trial will last approximately 18 months but this may vary for each individual. This includes a Screening Period of up to 21 days before receiving trial treatment, an estimated 5 months of treatment (the duration of treatment may vary for each participant), and approximately 12.5 months of follow up after trial treatment ends (the duration of follow up may vary for each participant).

Participation in the trial will require visits to the site, with more frequent visits during the first 6 weeks of treatment and then less frequent visits afterwards. At site visits, there will be various tests (such as blood draws) and procedures (such as recording of heart activity, computed tomography [CT] scans) to monitor whether the treatment is safe and effective. All participants will receive active drug; no one will be given placebo.

This is a first-in-human (FIH), Phase 1 open-label, multicenter, multinational trial in participants with certain types of solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of GEN1119.

Key Inclusion Criteria:

• Have histologically or cytologically confirmed diagnosis of protocol-specified solid tumours.
• Have progressed on standard of care (SoC) therapy applicable for the tumor type, or for whom there is no available SoC therapy likely to provide clinical benefit, and for whom experimental therapy with GEN1119 may be a suitable option in the opinion of the investigator.
• Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Have acceptable laboratory test results before GEN1119 administration per protocol

Key Exclusion Criteria:

• Prior treatment with certain protocol-defined therapy.
• Prior treatment with T-cell engagers, chimeric antigen receptor T-cell (CAR-T-cell) therapies, other protocol defined therapies, or other therapeutic moieties targeting certain protocol-defined molecules.
• Treatment with an anticancer agent within 4 weeks or within 5 half lives of the drug, whichever is shorter, but not within 2 weeks before Cycle 1 Day 1 (C1D1).
• Has clinically significant toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or lower, except for anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to ≤ Grade 2. There is no limitation for alopecia from previous therapies.
• Participant should not have active Hepatitis B infection. Participants with prior infections or chronic infections are allowed if monitored or treated as per local SOC and are negative for hepatitis B virus (HBV) DNA measured viral load.
• 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.

Randomization will not be used in Part 1 of this trial. Randomization will be incorporated into Part 2 cohorts and during Part 3 of the trial, randomization will be activated only if at least 2 recommended doses have been advanced from the preceding Parts 1 and/or 2.