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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ngm Biopharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

30 Mar 2026 → ongoing

Decision date (initial)

2025-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-521730-28-00

ClinicalTrials.gov

NCT07033026

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Efficacy

To evaluate the effect of NGM120 compared to placebo on body weight (Part A)
To evaluate safety and tolerability of NGM120 (Part B)

Secondary objectives 6

1. Key: To evaluate the effect of NGM120 compared to placebo on body weight (Part A)
2. To evaluate the effect of NGM120 compared to placebo on health-related quality of life (Part A)
3. To evaluate the safety and tolerability of NGM120 (Part A)
4. To assess the effects of NGM120 on body weight (Part B)
5. To evaluate PK of NGM120.
6. To evaluate immunogenicity.

Conditions and MedDRA coding

Colorectal Cancer with Cancer Cachexia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. 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.
2. 2. Documented histologic or cytologic diagnosis of CRC receiving standard of care treatment according to local/country specific practice guidelines (which may include systemic therapy).
3. 3. 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.
4. 5. Weigh at least 40 kg at enrollment (Study Day 1).
5. 6. Have ECOG PS 0-3.
6. 7. 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.
7. 4. 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.

Exclusion criteria 11

1. 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.
2. Receiving tube feedings or parenteral nutrition (either total or partial) at the time of Screening or Randomization.
3. 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).
4. Are planning to, or has undergone, major surgery within 28 days before Day 1.
5. Are pregnant or breastfeeding.
6. 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.
7. 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.
8. 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.
9. 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).
10. Have life expectancy <6 months.
11. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from baseline in body weight at Week 12
2. Treatment-emergent adverse events (TEAEs) characterized by type, frequency, severity, timing, seriousness, and relationship to study drug

Secondary endpoints 6

1. Key: Change from baseline in body weight at Week 16
2. Change from baseline over time in: − FAACT sub-scale scores (FAACT-ACS, FAACT-5IASS) − PROMIS (fatigue 7a & physical function 8c) − PGI-S and PGI-C (appetite and fatigue) − PGI-S and PGI-C (physical activity and walking)
3. Treatment-emergent adverse events (TEAEs) characterized by type, frequency, severity, timing, seriousness, and relationship to study drug
4. Change in body weight over time
5. Serum concentration and PK parameters of NGM120.
6. Incidence and titer of ADA and NAb over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ngm Biopharmaceuticals Inc.

Sponsor organisation

Ngm Biopharmaceuticals Inc.

Address

611 Gateway Boulevard Suite 540

City

South San Francisco

Postcode

94080-7017

Country

United States

Scientific contact point

Organisation

Ngm Biopharmaceuticals Inc.

Contact name

Vladimir Hanes, MD

Public contact point

Organisation

Ngm Biopharmaceuticals Inc.

Contact name

Vladimir Hanes, MD

Third parties 10

Locations

5 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications