GENMAB

A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination With Anti-cancer Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor

Subject must have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with
at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic
disease. Note: Subject must have received at least 2 doses of an approved anti-PD-1/PD-L1
mAb approved in NSCLC.

• Subject has progressed during or after treatment with 1 anti-PD-1/PD-L1 mAb
  administered either as monotherapy, or as SOC combination.
• Subject has progressed during or after platinum doublet chemotherapy following an
  anti-PD-1/PD-L1 mAb.
• Subject has progressed during or after an anti-PD-1/PD-L1 mAb following platinum
  doublet chemotherapy.

Subject must have PD-L1 tumor expression score of TPS ≥1% assessed by a central laboratory
during screening.

ECOG 0-1

Documentation of known EGFR, ROS1, or ALK mutations or gene rearrangements

• Subject has been exposed to any of the following prior therapies:
  • Prior treatment with docetaxel for NSCLC.
  • Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor vaccine, or
    autologous cell immunotherapy.
  • Treatment with an anti-cancer agent within 28 days prior to GEN1046 administration.
  • Any investigational agent for the treatment of stage 4 NSCLC.
  • Prior treatment with live, attenuated vaccines within 30 days prior to initiation of
    GEN1046.
  • Radiotherapy within 14 days prior to first GEN1046 administration.
  • Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg daily or
    a cumulative dose >150 mg prednisone within 14 days before the first GEN1046
    administration.
  • Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage
    colony stimulating factor support 4 weeks prior to first GEN1046 administration or being
    chronically transfusion dependent.
  • Subject received their last dose of anti-PD-1/PD-L1 mAb >250 days prior to enrollment in this
    trial.

  All subjects should undergo a CT scan or MRI of the brain to document new or existing central
  nervous system (CNS) lesions. Subjects with history of intracerebral arteriovenous
  malformation, cerebral aneurysm, progressive brain metastases, spinal cord compression (from
  disease), or stroke will be excluded.