Phase 3 study for people with Lung Cancer

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

• 18 years of age or older at screening.
• Have pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV)squamous or non-squamous NSCLC and not be a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer Tumor, lymph nodes, metastasis (TNM) staging system).
• Have tumor tissue available, either paraffin block or slides from a core, excisional or fine needle biopsy
• PD-L1 status available based on local testing results
• Measurable disease based on RECIST v1.1 per investigator.
• Eastern Cooperative Oncology Group performance status (ECOG) score of 0 or 1
• Expected survival ≥12 weeks

Exclusion Criteria:

• Participants with known actionable genomic alteration (AGAs), including estimated glomerular filtration rate (EGFR), anaplastic lymphoma kinase (ALK), Repressor of Silencing 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), rearranged during transfection (RET), and mesenchymal-epithelial transition (MET), for which there are available first-line therapies per local standard-of-care (SOC) are ineligible. Documented negative results for EGFR, ALK, and ROS1 AGAs are required for participants with non-squamous histology.

• Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter < 1 cm are permitted.

• Participants with clinically significant risk of hemorrhage or fistula are excluded.

• Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.

• Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1.

• Known to have a history of a severe allergy to any component of the study intervention, or a history of severe allergic reaction to chimeric or humanized antibody.

• History of allogeneic organ / hematopoietic stem cell transplantation.

• Participants with any of the following respiratory conditions:

• Evidence of noninfectious or drug-induced interstitial lung disease (ILD) or pneumonitis

• Grade ≥3 pulmonary disease unrelated to underlying malignancy

• History of uncontrolled comorbidities within 6 months prior to the first dose including uncontrolled cardiac and cerebrovascular conditions, hypertension, diabetes, significant vascular disease or arterial/severe venous thromboembolic events.

• Major surgery < 4 weeks or minor surgery < 3 days prior to first dose of study intervention.

• History of severe bleeding tendency or coagulation dysfunction

• History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.

• Participants with acute, chronic or symptomatic infections including participants positive for active HIV, hepatitis B virus (HBV), or Hepatitis C virus (HCV).

• Participants with history of immunodeficiency

• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior (in the past 5 years) or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.

• Previous systemic anti-tumor therapy including:

  1. Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.
  2. Previous treatment with immunotherapy
  3. Prior radiotherapy > 30 Gy to the lung < 6 months of first dose of study intervention
  4. Palliative local therapy < 2 weeks before the first dose of study intervention;
  5. Non-specific immunomodulatory therapy < 2 weeks before the first dose.
  6. Prior systemic anti-angiogenic therapy

• Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, adverse events from prior immunotherapy not improved to Grade 1 before screening, or required treatment with systemic immunosuppressive therapy.

• Prior and concomitant therapy:

  1. therapeutic oral or parenteral anticoagulants or thrombolytic agents < 10 days to the first dose.
  2. chronic antiplatelet therapy <7 days to randomization.
  3. live or attenuated live vaccine < 4 weeks to the first dose.
  4. current high-dose systemic corticosteroids.
  5. prohibited concomitant medication(s) < 21 days to the first dose.

• Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.