Ponsegromab for Cachexia

(PROACC-1 Trial)

No longer recruiting at 138 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Disqualifiers: Tube feedings, Parenteral nutrition, Renal disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ponsegromab, an experimental drug, to determine if it helps people with cachexia—a condition causing severe weight loss and muscle wasting—linked to cancer feel better. Researchers aim to assess the safety and effectiveness of ponsegromab compared to a placebo in individuals with certain cancers, such as lung, pancreatic, or colorectal cancer, who also have high levels of a specific protein called GDF-15. The study includes different groups trying various doses of ponsegromab to identify the most effective dose. Suitable participants are those with cancer-related cachexia who are not receiving certain types of nutritional support, like tube feedings. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ponsegromab is usually well-tolerated. In one study, patients who took ponsegromab did not experience serious side effects. The treatment reduced levels of a protein called GDF-15, which is linked to weight loss in cancer patients. Another study found that patients taking ponsegromab gained weight, increased muscle mass, and improved their quality of life. These results suggest that ponsegromab is safe for humans at various doses. However, discussing potential risks with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for cachexia?

Unlike existing treatments for cachexia, which often involve nutritional supplements or appetite stimulants, Ponsegromab offers a novel approach by targeting underlying biological pathways. Ponsegromab is unique because it is administered through a subcutaneous injection and comes in low, medium, and high doses, allowing for tailored treatment options. Researchers are particularly excited about its potential to directly influence muscle wasting, a key challenge in cachexia management, offering hope for more effective intervention.

What evidence suggests that this trial's treatments could be effective for cachexia?

Research has shown that ponsegromab holds promise for treating cancer cachexia, a condition that causes weight loss and muscle wasting. In this trial, participants will receive varying doses of ponsegromab or a placebo. Studies found that those taking ponsegromab gained weight, increased muscle mass, and improved physical function. Participants also experienced better appetites and quality of life. Ponsegromab blocks a protein called GDF-15, which is linked to weight loss and muscle wasting. This suggests that ponsegromab could help patients remain strong and energetic during cancer treatment. The evidence supports its potential as an effective treatment for cachexia. ^{2 3 4 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung, pancreatic, or colorectal cancer who are experiencing cachexia (significant weight loss due to illness) as defined by Fearon criteria. They must have elevated GDF-15 protein levels and be able to consent to the study. People with tube feedings, other causes of cachexia, severe allergies to monoclonal antibodies, or poor kidney/liver function cannot join.

Inclusion Criteria

Serum GDF-15 concentrations

Signed informed consent

I have significant weight loss and muscle loss.

Exclusion Criteria

My weight loss is not due to cancer.

I am currently on tube feedings or IV nutrition.

You have temporary reasons that are causing you to eat less.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ponsegromab or placebo subcutaneously every 4 weeks for 12 weeks

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of ponsegromab treatment every 4 weeks for up to one year

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Placebo for Ponsegromab
• Ponsegromab

Trial Overview

The trial is testing the effectiveness and safety of a drug called Ponsegromab in comparison to a placebo in patients suffering from cancer-related cachexia. Participants will either receive Ponsegromab or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab medium dose subcutaneous injection every 4 weeks

Group II: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab low dose subcutaneous injection every 4 weeks

Group III: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab high dose subcutaneous injection every 4 weeks

Group IV: Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment Placebo Group 1 Intervention

Match placebo subcutaneous injection every 4 weeks

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a phase Ib study involving 10 patients with advanced cancer and cachexia, ponsegromab was well tolerated with no significant adverse effects, indicating its safety for use in this population.

Ponsegromab effectively reduced serum GDF-15 levels and led to an average weight increase of 4.63 kg (about 6.6% from baseline) over 12 weeks, along with improvements in physical activity and quality of life, suggesting its potential efficacy in treating cachexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia. Crawford, J., Calle, RA., Collins, SM., et al.[2023]

In a study of 13 patients with advanced cancer cachexia, a combination of the anabolic β2-agonist formoterol and the appetite stimulant megestrol acetate was found to be safe and well tolerated over an 8-week period, with few adverse reactions reported.

Of the patients who completed the treatment, 86% showed significant improvements in muscle size and/or function, indicating that this combination therapy could effectively address muscle loss in cancer cachexia and should be explored further in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Greig, CA., Johns, N., Gray, C., et al.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39282907/

Ponsegromab for the Treatment of Cancer Cachexia

Ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed ...

2.

pfizer.com

pfizer.com/news/press-release/press-release-detail/pfizer-presents-positive-data-phase-2-study-ponsegromab

Pfizer Presents Positive Data from Phase 2 Study of ...

This study showed us those who received ponsegromab had improvement in body weight, muscle mass, quality of life, and physical function.

3.

nejm.org

nejm.org/doi/abs/10.1056/NEJMoa2409515

Ponsegromab for the Treatment of Cancer Cachexia

Ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05546476

NCT05546476 | Study of the Efficacy and Safety ...

A 12 week double blind study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and ...

5.

nature.com

nature.com/articles/d41573-025-00168-x

Cancer cachexia contender enters first pivotal trial

Cachexia results in decreased appetite and the loss ... Pfizer's phase II trial of ponsegromab recruited 187 patients with cancer cachexia ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37982848/

A Phase Ib First-In-Patient Study Assessing the Safety, ...

Ponsegromab was well tolerated, suppressed serum GDF-15 concentrations, and demonstrated preliminary evidence of efficacy.

7.

medchemexpress.com

medchemexpress.com/ponsegromab.html?srsltid=AfmBOoqB6ZRQiTqGw6jCOzgomsAaLO8fEFCKLk3mHWtsfqadIm7EYpUy

Ponsegromab (PF 06946860) | Humanized Anti-GDF15 ...

Ponsegromab (PF 06946860) is a potent and selective humanized anti-GDF15 monoclonal antibody with anti-cachexia activity.