A Phase 2/3 interventional study of ponsegromab and placebo in Cachexia and Metastatic Pancreatic Ductal Adenocarcinoma, sponsored by Pfizer. Recruiting at 230 sites in 21 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-14.
Sponsored by Pfizer · Phase 2/3, Interventional, and Treatment
Study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and metastatic pancreatic ductal adenocardinoma.
A Phase 2b/3, randomized, double-blind, multicenter, multinational study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and mPDAC. The first-line chemotherapies will either be nab-paclitaxel plus gemcitabine or FOLFIRINOX (or mFOLFIRINOX). The double-blind period is followed by an optional open-label extension period.
Initial enrollment will be in Phase 2b. If all eligibility criteria are met, participants will be randomized in a 1:1:1 allocation to study intervention (one of the two doses of ponsegromab, or placebo) plus first-line systemic chemotherapy. Participants must have completed their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-days cycles of FOLFIRINOX) prior to the start of receiving their first dose (Day 1) of study intervention (ponsegromab or placebo). Day 1 study intervention must be taken on the same day participants start their next cycle of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy. All chemotherapy dosing is to be determined by the participant's health care provider in accordance with local guidelines. Study intervention will be administered Q4W SC.
Following enrollment completion of Phase 2b, Phase 3 enrollment will begin, and eligible participants will be randomized in a 1:1:1 allocation to study intervention (one of the two doses of ponsegromab, or placebo). Participants must have completed their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-day cycles of FOLFIRINOX) prior to the start of receiving their first dose (Day 1) of study intervention (ponsegromab or placebo). Day 1 study intervention must be taken on the same day participants start their next cycle of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy. All chemotherapy dosing is to be determined by the participant's health care provider in accordance with local guidelines. Study intervention will be administered Q4W SC.
Once all Phase 2b participants have completed Week 12 procedures, an analysis of Phase 2b will be performed, from which one of the 2 ponsegromab doses will be selected. After the Phase 3 ponsegromab dose has been selected, continuing Phase 2b participants will:
After the ponsegromab dose has been selected, continuing Phase 3 participants will:
During the Phase 3 portion of the study, there will be an optional sub-study for primary caregivers of participants with cachexia and mPDAC to evaluate the effectiveness of ponsegromab in improving the quality of life and well-being of the primary caregivers.
Study intervention (ponsegromab selected dose or placebo) will continue regardless of chemotherapy treatment until permanent discontinuation of study intervention, withdrawal of consent, death, or the end of the Phase 3 double-blind portion of the study has been reached when the approximate number of overall survival events have been accrued for the Phase 3 analysis of overall survival.
Participants will have tumor assessments performed approximately every 6 to 8 weeks during the double-blind period by blinded, independent, central reader radiologists.
When the number of overall survival events has been accrued to terminate the Phase 3 double-blind portion of the study, active participants can continue in the optional open-label extension where they will receive ponsegromab for up to 12 months.
331 studies on the registry are indexed under Cachexia; 75 are open to participants now.
This study's planned enrollment of 982 is above the median of 74 across 226 interventional studies indexed under Cachexia.
Browse Cachexia studies →Pfizer is the lead sponsor of 3,334 studies on the registry; 149 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 391 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ponsegromab 200 mg subcutaneous injection every 4 weeks
Drug: ponsegromab
ponsegromab 400 mg subcutaneous injection every 4 weeks
Drug: ponsegromab
Match placebo subcutaneous injection every 4 weeks
Drug: placebo
Double-Blind ponsegromab Treatment
Double-Blind placebo Treatment
Percent change from baseline in body weight for ponsegromab compared to placebo
Time frame: Baseline, Week 12
Change from baseline in Functional Assessment of Anorexia/Cachexia Therapy 5-item Anorexia Symptom Scale scores
Scale consists of five items, each rated 0-4. Total score ranges from 0 (minimum) to 20 (maximum). Higher scores are associated with a better outcome.
Time frame: Baseline, Week 12
Change from baseline in non-sedentary physical activity time
measured by wearable Digital Health Technology watch
Time frame: Baseline, Week 12
Overall survival
Outcome defined as the time from randomization to occurrence of all-cause death
Time frame: Randomization through completion of Phase 3 of the study, an average of 1 year
Change from baseline in body weight (kg)
Time frame: Baseline, Week 12 and up to Week 52
Change from baseline at Week 12 in physical activity as measured by total vector magnitude
measured by wearable Digital Health Technology watch
Time frame: Baseline, Week 12
Effect on progression free survival
determined by Blinded Independent Central Review
Time frame: Randomization through completion of Phase 3 of the study, an average of 1 year
Effect on objective response rate
determined by Blinded Independent Central Review
Time frame: Baseline, Week 52
Effect on disease control rate
determined by Blinded Independent Central Review
Time frame: Baseline, Week 52
Effect on duration of response
determined by Blinded Independent Central Review
Time frame: Baseline, Week 52
Change from baseline in skeletal muscle area and radiodensity at third lumbar vertebra (L3)
measured by CT (or MRI) scan
Time frame: Baseline, Week 12
Change from baseline in intermuscular adipose area and radiodensity at L3
measured by CT (or MRI) scan
Time frame: Baseline, Week 12
Change from baseline in subcutaneous adipose area and radiodensity at L3
measured by CT (or MRI) scan
Time frame: Baseline, Week 12
Change from baseline in visceral adipose area and radiodensity at L3
measured by CT (or MRI) scan
Time frame: Baseline, Week 12
Number of participants with incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to permanent discontinuation from study intervention or from study.
Time frame: Baseline, Week 12 and up to Week 52
Number of participants with laboratory test abnormalities.
Time frame: Baseline, Week 12 and up to Week 52
Number of participants with vital signs abnormalities.
Time frame: Baseline, Week 12 and up to Week 52
Change in physical function, assessed on participant completed Patient-Reported Outcomes Measurement Information System Physical Function (version 8c) questionnaire.
The overall score range for the T-score is 0-100. Higher scores indicate better outcome.
Time frame: Baseline, Week 12 and up to Week 52
Change in fatigue, as assessed on participant completed Patient-Reported Outcomes Measurement Information System - Fatigue (version 7a) questionnaire.
The overall score range for the T-score is 29.4-83.2. Lower scores indicate better outcome.
Time frame: Baseline, Week 12 and up to Week 52
Occurrence and severity of symptomatic AEs including diarrhea, nausea, vomiting, decreased appetite, fatigue and mouth sores by maximum grade as assessed by the NCI PRO CTCAE.
Time frame: Baseline, Week 52
Change from baseline on ECOG PS
Time frame: Baseline, Week 12 and up to Week 52
Occurrence of chemotherapy dosing changes (including dosing reductions, dosing interruptions, and dosing discontinuations) due to occurrence of the TEAEs of nausea, vomiting, diarrhea, loss of appetite, or fatigue
Time frame: Baseline, up to Week 52
Tumor status
Assessment of tumor response to treatment as determined by Blinded Independent Central Review assessment per RECIST 1.1 using CT scan (or MRI)
Time frame: Baseline, Week 12 and up to Week 52
Showing the first 100 of 230 sites across 21 countries. Choose a country and city above to see the rest.
Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Data sharing details ↗ · www.pfizer.com
Started Oct 2025 (actual). Primary completion is estimated for Jan 2028, 27 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ponsegromab