Efficacy and Safety of NGM120 in Colorectal Cancer Patients with Cancer Cachexia: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2025-521730-28-00
Protocol: 120-CX-202
Sponsor: Ngm Biopharmaceuticals Inc.

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Diseases & Conditions

Colorectal cancer Cachexia

Objectives

The primary objective of this study is to evaluate the efficacy of NGM120 compared to placebo on body weight in participants with colorectal cancer experiencing cancer cachexia (5). Additionally, the study aims to assess the safety (4) and tolerability (13) of the investigational product. Secondary objectives include:

Evaluation of NGM120 effects on body weight (5)
Assessment of health-related quality of life (5)
Evaluation of safety (4) and tolerability (13)
Assessment of pharmacokinetics (6)
Evaluation of immunogenicity

Participants

This clinical trial involves 82 participants diagnosed with colorectal cancer accompanied by cancer cachexia. The study population includes both male and female patients within specified age ranges. Eligible individuals must have a documented histologic or cytologic diagnosis and be receiving standard of care treatment. Inclusion requires the presence of cachexia as defined by Fearon criteria, characterized by specific parameters of body mass index, involuntary weight loss, or sarcopenia. Participants must weigh at least 40 kg and possess an ECOG performance status of 0-3. Additionally, subjects are selected if they have exhausted or have contraindications to existing treatments intended to increase appetite or body weight. The objectives are:

To evaluate the effect of NGM120 compared to placebo on body weight
To evaluate the safety and tolerability of NGM120

Plans and Procedures

This Phase 2, multicenter, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, and tolerability of NGM120, a humanised IgG1 monoclonal antibody against GDNF family receptor alpha-like, in participants with colorectal cancer experiencing cancer cachexia. The research is divided into two parts: Part A assesses the effect of the investigational product on body weight, while Part B evaluates safety and tolerability. Participants will receive either NGM120 via subcutaneous injection or a placebo. The study methodology includes a screening visit to assess eligibility based on histologic diagnosis, body mass index, and sarcopenia criteria. Following enrollment, the primary endpoint is the change from baseline in body weight at Week 12, with additional assessments at Week 16 to evaluate secondary outcomes such as pharmacokinetics and treatment-emergent adverse events. The study also monitors patient-reported outcomes regarding appetite, fatigue, and physical function. Participant involvement includes regular follow-up visits to monitor safety and efficacy until the end-of-study procedures are completed.

Treatment

NGM120 is a humanised IgG1 monoclonal antibody against GDNF family receptor alpha-like. The experimental medication is administered as a 200 mg injection via the subcutaneous route.

The control group receives a placebo for NGM120.

Efficacy

The assessment of efficacy in participants with colorectal cancer and cancer cachexia focuses on the evaluation of body weight. The primary endpoint is the change from baseline in body weight at Week 12. Secondary efficacy endpoints include the change from baseline in body weight at Week 16 and the change in body weight over time.

Additional efficacy evaluations involve changes from baseline over time in several patient-reported outcomes. These include:

FAACT sub-scale scores, specifically FAACT-ACS and FAACT-5IASS.
PROMIS scores for fatigue and physical function.
PGI-S and PGI-C assessments for appetite, fatigue, physical activity, and walking.

The study also monitors serum concentration and pharmacokinetic parameters of NGM120, as well as the incidence and titer of anti-drug antibodies and neutralizing antibodies over time.

Inclusion and Exclusion Criteria

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Inclusion Criteria

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 CRC receiving standard of care treatment according to local/country specific practice guidelines (which may include systemic therapy).
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 40 kg at enrollment (Study Day 1).
Have ECOG PS 0-3.
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.

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Exclusion Criteria

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; • NCI CTCAE Grade 3 or 4 gastrointestinal (GI) disorders (nausea, vomiting, diarrhea, and constipation); • Mechanical obstructions making the participant unable to eat.
Receiving tube feedings or parenteral nutrition (either total or partial) at the time of Screening or Randomization.
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 • New York Heart Association (NYHA) Class III-IV heart failure; or • Acquired immunodeficiency syndrome (AIDS).
Are planning to, or has undergone, major surgery within 28 days before Day 1.
Are pregnant or breastfeeding.
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.
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.
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.
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 life expectancy <6 months.
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).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Recruiting	30 Sept 2025	11
Czechia	Recruiting	30 Sept 2025	9
Hungary	Recruiting	30 Sept 2025	9
Poland	Recruiting	30 Sept 2025	16
Slovakia	Recruiting	30 Sept 2025	9