The purpose of this trial is to learn about the safety and effectiveness of the antibody GEN1079 in participants with certain types of cancer.

The trial has multiple parts. The first part of the trial tests different doses of GEN1079 to find out if it is safe and determine what are the best doses to use. The second and third parts continue to test the safety of and whether GEN1079 works in additional participants with specific cancer types and at doses chosen based on results from the previous parts of the trial.

For each participant, the trial will last approximately 33 to 67 weeks but this may vary for each person. This includes up to 21 days for screening prior to receiving trial treatment, approximately 6 to 12 weeks of treatment (the duration of treatment may vary for each participant), and approximately 24 to 52 weeks of follow up after trial treatment ends (the duration of follow up may vary for each participant). During the screening, tumor tissue either collected prior to this trial or freshly collected during screening will be provided by all participants.

Participation in the trial will require visits to the site, with more frequent visits at the start 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, multinational, dose escalation and expansion trial in participants with advanced selected solid tumors.

Key Inclusion Criteria:

All Parts:

• Must have histologically confirmed selected solid cancers.
• Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The measurable lesion(s) must be outside the field of prior radiation therapy unless there is documented progression in the lesion(s).
• Must provide formalin-fixed paraffin-embedded tumor tissue (aspirates and bone specimens are not acceptable), archival or fresh, collected after discontinuation of their most recent anticancer treatment and prior to the first administration of GEN1079. If an archival specimen is unavailable, a procedure for obtaining a fresh tumor biopsy must be performed, provided it is performed according to standard of care and is deemed safe by the investigator.
• Has acceptable laboratory test results prior to trial treatment administration, including platelet count >150×10^9/litre (L).

Parts 1 and 2:

• Have histologically confirmed selected solid cancers that are metastatic or unresectable.
• Prior protocol defined therapy is permitted, with no restrictions on the number of prior lines of therapy received or the time since the most recent therapy.

Part 3:

• Have histologically confirmed selected solid cancer that is metastatic or unresectable.
• Must have received a defined number of prior lines of a protocol defined regimen.

Key Exclusion Criteria:

• Has intercurrent illness or known history of any of the following that could affect compliance with the protocol or interpretation of the results, including but not limited to:

  • Autoimmune diseases, eg, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), neuromyelitis optica (NMO), myasthenia gravis (MG), cold agglutinin disease (CAD), atypical hemolytic uremic syndrome (aHUS), immunoglobulin A (IgA) nephropathy, inflammatory bowel disease (IBD; Crohn's and ulcerative colitis).
  • Grade ≥3 allergic reactions to prior monoclonal antibody therapy.
  • Known history of interstitial lung disease (ILD) Grade ≥3 or prior or ongoing noninfectious pneumonitis with evidence of progressive fibrotic changes on baseline imaging, unless clinically and radiologically stable for ≥6 months with preserved pulmonary function (eg, diffusing capacity of the lungs for carbon monoxide [DLCO] ≥ 50% predicted).
  • Disorders associated with platelet function defects, decreased number of platelets (eg, splenomegaly, chronic liver disease or bleeding disorders such as hemophilia or Von Willebrand disease), or a known history or high risk of bleeding events requiring transfusions or hospitalizations.

• Treatment with any plasma-based therapy within 7 days prior to Cycle 1 Day 1.

• Any history of intracerebral arteriovenous malformation (shunts), cerebral aneurysm, spinal cord compression (from disease), carcinomatous meningitis, or stroke. Note: Transient ischemic attack >1 month prior to screening is allowed.

• Participants who, in the event of a medical complication during the trial treatment period, would be unable to temporarily discontinue and restart anticoagulant/antiplatelet therapy using appropriate bridging strategies (eg, low molecular weight heparin) in alignment with local standard of care.

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

In the dose escalation part (Part 1), participants will not be randomized. If more than 1 dose level (DL) is explored in the dose refinement part (Part 2) and Expansion (Part 3), participants will be randomized across the selected DLs.