The purpose of this trial is to learn about the safety and effectiveness of GEN1106 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 tests different doses of GEN1106 to find out if it is safe and determine what are the best doses to use. The second and third parts continues to test the safety of and how well GEN1106 works in additional participants with a specific cancer type and at doses chosen based on results from the first part of the trial.

For each participant, the trial will last approximately 17 months but will vary for each person. This includes up to 21 days for screening prior to receiving trial treatment, approximately 5 months of treatment (the duration of treatment may vary for each participant), and approximately 11 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), open-label, multicenter, dose escalation and expansion trial in participants with urothelial and other cancers who have metastatic disease to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of GEN1106.

Key Inclusion Criteria:

• Have progressed on or after standard of care (SoC) therapy, which should include chemotherapy, anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapies, and enfortumab vedotin (EV), 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 GEN1106 may be beneficial, in the opinion of the investigator.
• Have measurable disease according to RECIST v1.1.
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1 at screening.
• Part 1: Have histologically or cytologically confirmed diagnosis of cancer as specified per protocol.
• Parts 2 and 3: Have histologically or cytologically confirmed diagnosis of metastatic urothelial carcinoma (mUC).

Key Exclusion Criteria:

• Prior treatment with topoisomerase 1 inhibitor-based antibody-drug conjugate (ADC) therapy.
• 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.
• Has clinically significant toxicities from previous anticancer therapies that have not resolved to baseline levels or to grade 1 or lower, except for alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to grade 2.

Note: Other protocol-defined Inclusion and Exclusion criteria may apply.

Randomization will not be used for the Dose Escalation part. In the Dose Refinement and Expansion parts, randomization may be used.