A Study to Learn About the Study Medicine Called Ponsegromab in Adults With Lung Cancer-Associated Significant Body Weight Loss

Prior treatment

• Receiving tube feedings or having an ongoing clinical indication for parenteral nutrition (either total or partial) at the time of screening or randomization. Of note: short-term parenteral nutritional support for the management of acute, transient medical indications is allowed if discontinued prior to randomization.
• Clinically significant ascites that requires medical intervention or underwent a paracentesis within 4 weeks prior to randomization.
• Undergoing major surgery within 4 weeks prior to randomization or planned major surgical procedures during the study.
• Chronic use of systemic corticosteroid.
• Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to:
  • Severe asthma requiring systemic corticosteroids within 30 days prior to first dose of study intervention or not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists.
  • Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids.
  • Clinically severe and/or Grade 4 pulmonary emboli within 3 months of the first dose of study intervention. Pulmonary emboli in main or lobar pulmonary arteries are also excluded.
  • Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc).

Other illness

• Mixed small cell and non-small cell lung cancer histology.
• History of adrenal disorders (e.g. adrenal insufficiency, Cushing syndrome), pituitary adenoma or ectopic ACTH.
• History of any secondary malignancy in the last 2 years, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ.
• Symptomatic brain metastasis or leptomeningeal disease.

Lab values

• Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification.
• Renal disease requiring dialysis or eGFR \<30 mL/min/1.73 m².
• History of severe liver disease or cirrhosis, unrelated to metastatic cancer. LFT abnormalities at the time of screening; confirmed by a single repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN (\>5 x ULN if liver involvement by the tumor), or total bilirubin level ≥ 1.5 x ULN (For Gilbert's syndrome, direct bilirubin \> ULN is exclusionary).
• Left ventricular ejection fraction \<50% on screening echocardiogram (or MUGA scan).

Other

• Current active reversible causes of decreased food intake, as determined by the investigator. These causes may include, but are not limited to:
  • NCI CTCAE Grade 3 or 4 oral mucositis
  • Mechanical obstructions interfering with the participant's ability to eat
• Cachexia caused by reasons other than NSCLC, as determined by the investigator (eg, severe COPD).

• Signed Informed Consent
• Documented histological or cytologic diagnosis of NSCLC with each of the following:
  • locally advanced, unresectable, stage III disease (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer TNM staging system); and
  • measurable disease at time of screening (assessment per RECIST v1.1); and
  • must have completed platinum-based chemotherapy concurrent with radiation therapy, within 7 to 42 days prior to the randomization; and
  • no evidence of progression of disease following definitive, platinum-based, concurrent chemoradiation therapy; and
  • must be due to receive consolidation immunotherapy with durvalumab for up to 12 months, with the first dose of blinded study intervention to coincide with the first dose of durvalumab +/- 7 days; and
  • absence of actional genomic mutations (eg, EGFR, ALK).
• Cachexia defined by Fearon criteria:
  • BMI \<20 kg/m2 and involuntary weight loss of \>2% within 6 months prior to screening; or
  • Involuntary weight loss of \>5% over the past 6 months prior to screening irrespective of BMI
• Participant has been evaluated and determined that available anticachexic treatments have either been administered with no positive effect or the participant is not suitable for these treatments.
• Participants who are assessed by the investigator to have an ECOG PS ≤1.