A multi-center evaluation of NGM120 in a randomized, double-blind, placebo-controlled study in participants with colorectal cancer who have cancer cachexia.

Prior treatment

• Are being initiated on new treatment with systemic glucocorticoids within the 4 weeks prior to the first dose of NGM120; stable (ie, no significant change to dosage or frequency of administration in prior 4 weeks) steroid therapy (eg, dexamethasone) as part of pre-medication or daily oral prednisone is permissible.
• Participated in another investigational drug study with NGM120 or any other experimental therapy targeting glial cell-derived neurotrophic factor family receptor α-like (GFRAL) or growth differentiation factor 15 (GDF15).
• Receiving tube feedings or parenteral nutrition (either total or partial) at the time of Screening or Randomization.
• Are planning to, or has undergone, major surgery within 28 days before Day 1.
• Have prior allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (immunoglobulin G [IgG] protein) or molecules made of components of a monoclonal antibody.

Other illness

• Have current active reversible causes of decreased food intake, as determined by the Investigator. These causes may include, but are not limited to the following: National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 oral mucositis, diarrhea; Mechanical obstructions making the participant unable to eat.
• Have active brain metastases or leptomeningeal disease.
• Have cachexia caused by other reasons, as determined by the Investigator, including, but not limited to: Severe chronic obstructive pulmonary disease (COPD) requiring use of home O2; or Acquired immunodeficiency syndrome (AIDS).
• Have any other significant medical, psychiatric, substance abuse problem, or history of suicidal ideation that would preclude participation in the study per Investigator’s assessment.

Lab values

• Have elevated liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥3.0×ULN, or ≥5.0×ULN if there is liver involvement by the tumor).
• Have history of New York Heart Association (NYHA) Class III-IV heart failure; or left ventricular ejection fraction of <50% within 12 months before Study Day 1.
• Have history of renal disease requiring dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.

Other

• Have BMI >30 kg/m2.
• Have ascites requiring repeated paracentesis.
• Have life expectancy <6 months.
• Are pregnant or breastfeeding.

• Must be at least 18 years of age, who comprehend and are willing to sign an Informed Consent Form (ICF), at the time of the Screening visit.
• Documented histologic or cytologic diagnosis of Stage 4 CRC receiving standard of care treatment according to local/country specific practice guidelines (which may include systemic therapy). Discuss with the Sponsor if a potential study participant has < Stage 4 CRC.
• Cachexia defined by Fearon criteria as at least one of the following: • Body mass index (BMI) <20 kg/m2 with involuntary weight loss of >2% within 6 months prior to enrollment; or Current involuntary weight loss of >5% which has not improved over the past 6 months prior to enrollment, irrespective of BMI; or Sarcopenia as defined by appendicular skeletal muscle index (males <7.26 kg/m2 or females <5.45 kg/m2) with involuntary weight loss of >2% within 6 months prior to enrollment, irrespective of BMI.
• Weigh at least 30 kg at enrollment on Study Day 1.
• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2. Discuss with the Sponsor if a potential study participant has an ECOG of 3.
• Male participants who are sexually active with a female partner of childbearing potential and female participants of childbearing potential must agree to use adequate birth control in consultation with Investigator from Screening to 4 months after the last dose of study drug. Refer to Section 6.9 on contraception methods.
• Participants will be included in the study if they have exhausted all treatment options intended to increase appetite or body weight, have clear contraindications to such treatments, or cannot be administered these treatments for any other reasons based on the local standard-of-care or treatment availability per the Investigator.