Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer

Key Inclusion Criteria:

• Have signed an informed consent form (ICF)

• Be at least 18 years of age.

• Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with atleast 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb formetastatic disease

• Have a tumor PD-L1 expression result available prior to first treatmentdemonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central orlocal laboratory during screening.

• Have measurable disease per RECIST v1.1.

• Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.

• Have life expectancy of at least 3 months.

• Have adequate organ and bone marrow function as defined in the protocol.

Key Exclusion Criteria:

• Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions,RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14skipping. Note: Subjects harboring such mutations, gene rearrangements oramplifications may be enrolled in the trial, if subjects have received priorapproved targeted therapy for such mutations, the subject may still be eligible forthis trial.

• Treatment with an anti-cancer agent within 28 days prior to acasunlimabadministration.

• Any investigational agent (including investigational vaccines).

• Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliativeradiotherapy will be allowed for local pain control under certain conditions.

• Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg dailyor a cumulative dose >150 mg prednisone within 14 days before the first acasunlimabadministration.

• Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

• Subject has contraindications to the use of pembrolizumab per local prescribinginformation.

• Subject has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis (interstitial lung disease).

• Ongoing or active infection requiring intravenous treatment with anti-infectivetherapy or any ongoing systemic inflammatory condition requiring further diagnosticwork-up or management during screening.

• Symptomatic congestive heart failure (grade III or IV as classified by the New YorkHeart Association), unstable angina pectoris, or cardiac arrhythmia.

• Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/ordiastolic blood pressure ≥100 mmHg, despite optimal medical management.

• Ongoing or recent (within 6 months) evidence of significant autoimmune disease thatrequired treatment with systemic immunosuppressive treatments, which may suggestrisk for irAEs.

• Subject has a known history of any of the following:

1. Grade 3 or higher irAEs that led to treatment discontinuation of a priorimmunotherapy treatment.

2. Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.

3. Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis,drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).

4. Organ allograft (except for corneal transplant) or autologous or allogeneicbone marrow transplant, or stem cell rescue within 3 months prior to the firstdose of acasunlimab.

5. Grade 3 or higher allergic reactions to monoclonal antibody therapy as well asknown or suspected allergy or intolerance to any agent given in the course ofthis trial.

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