GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors

Key Inclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Participants with non-CNS solid tumors that is metastatic or unresectable and forwhom there is no available standard therapy.

• Participants with a confirmed diagnosis of relapsed or refractory, advanced and/ormetastatic melanoma, NSCLC, or CRC and for whom there is no available standardtherapy

Combination Therapy - Dose Expansion Part

• Participants with unresectable Stage III or Stage IV melanoma with no prior systemicanticancer therapy for unresectable or metastatic disease. Primary ocular or mucosalmelanoma is excluded.

• Participants with Stage IV metastatic or recurrent NSCLC with no prior systemicanticancer therapy, no actionable mutation.

• Participants with recurrent or metastatic HNSCC with no prior systemic therapyadministered in the recurrent or metastatic setting.

• Participants with confirmed metastatic PDAC with no previous radiotherapy, surgery,chemotherapy, or investigational therapy for the treatment of metastatic disease.

General (all phases):

• Must be age ≥ 18 years of age on the day of signing informed consent, or the legalage of consent in the jurisdiction in which the trial is taking place.

• Measurable disease according to RECIST 1.1

• Eastern Cooperative Oncology Group (ECOG) 0-1

• Normal or adequate liver, renal, cardiac and bone marrow function

Key Exclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Treatment with an anti-cancer agent (within 21 days or after at least 5 half-livesof the drug, whichever is shorter), prior to GEN1042 administration

• Radiotherapy within 14 days prior to first GEN1042 administration

• Toxicities from previous anti-cancer therapies that have not resolved

Combination Therapy - Dose Expansion Part

• Has received prior systemic cytotoxic chemotherapy, biological therapy, OR majorsurgery within 3 weeks or at least 5 half-lives of the drug (whichever is shorter)of the first dose of trial treatment.

• Radiotherapy within 14 days of start of trial treatment or received lung radiationtherapy of > 30 Gy within 6 months of the first dose of trial treatment.

General (all phases)

• Participants has an active, known, or suspected autoimmune disease.

• History of non-infectious pneumonitis that required steroids or currently haspneumonitis.

• History of ≥ grade 3 allergic reactions to monoclonal antibody (mAb) therapy

• Participants with a condition requiring systemic treatment with eithercorticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressivemedications within 14 days of first treatment.

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