PONSEGROMAB for Cancer cachexia|Metastatic pancreatic ductal adenocarcinoma

Inclusion criteria

• {"criterion_text":"-Aged ≥18 years of age (or the minimum age of consent in accordance with local regulations if >18 years) at the Screening Visit."}
• {"criterion_text":"-Documented histologic or cytologic active diagnosis of mPDAC (locally advanced disease is not eligible) •\tMeasurable disease; participant has one or more metastatic tumors measurable by CT scan (or MRI, if patient is allergic to CT contrast media) according to RECIST v 1.1. and: •\tCompleted 1 × 28-day cycle of first-line systemic nab-paclitaxel and gemcitabine chemotherapy or 2 × 14-day cycles of FOLFIRINOX chemotherapy and must be prior to receiving the next cycle of nab-paclitaxel plus gemcitabine chemotherapy or FOLFIRINOX chemotherapy."}
• {"criterion_text":"-Cachexia as defined by Fearon criteria (see Section 8.1.1 for details on documented body weight from medical records): •\tBMI < 20 kg/m2 and involuntary weight loss of > 2% within 6 months prior to screening •\tInvoluntary weight loss of >5% over the past 6 months prior to screening irrespective of BMI"}
• {"criterion_text":"-Participants who are assessed by the investigator to have: •\tan ECOG PS ≤1 and •\ta life expectancy of ≥4 months."}
• {"criterion_text":"-Evidence of personally signed and dated ICD indicating that the participant has been informed of and comprehended all pertinent aspects of the trial."}
• {"criterion_text":"-Participant has been evaluated and determined that available anticachexic treatments have either been administered with no positive effect or the participant is not suitable for these treatments."}

Exclusion criteria

• {"criterion_text":"-Medical Conditions: Current active reversible causes of decreased food intake, as determined by the investigator. These causes may include, but are not limited to: •\tNCI CTCAE Grade 3 or 4 oral mucositis •\tNCI CTCAE Grade 3 or 4 GI disorders (nausea, vomiting, diarrhea, and constipation) •\tMechanical obstructions interfering with the participant's ability to eat"}
• {"criterion_text":"-History of severe liver disease or cirrhosis, unrelated to metastatic cancer. Potential participants with the following liver function test abnormalities will also be excluded; results may be confirmed by a single repeat test, if necessary: •\tTotal bilirubin ≥1.5 × ULN (For Gilbert’s syndrome, direct bilirubin >ULN is exclusionary) •\tAST 3 × ULN (AST  5× ULN if there is liver involvement by the tumor) •\tALT 3 × ULN (ALT 5× ULN if there is liver involvement by the tumor) •\tAlkaline phosphatase 3 x ULN (Alkaline phosphatase 5× ULN if there is liver involvement by the tumor and/or in case of bone metastases, or if considered related to prior surgery eg, pancreaticoduodenectomy)."}
• {"criterion_text":"-Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >470 ms)."}
• {"criterion_text":"-Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma."}
• {"criterion_text":"-Symptomatic brain metastasis or leptomeningeal disease."}
• {"criterion_text":"-Prior/Concomitant Therapy: Participants must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with chemotherapy in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no persistence of treatment-related toxicities are present."}
• {"criterion_text":"-Current use of any prohibited concomitant medication(s) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study intervention. Refer to Section 6.9 for full details of prohibited and permitted medications."}
• {"criterion_text":"-Prior/Concurrent Clinical Study Experience: Previous administration with an IP (drug, biologic agents, or vaccine) either within 30 days (or as determined by the local requirement) or 5 half lives, whichever is longer, preceding the first dose of study intervention used in this study through the duration of the study."}
• {"criterion_text":"-Previous participation in a clinical study evaluating ponsegromab (including exposure to placebo)."}
• {"criterion_text":"-Diagnostic Assessments: Renal disease requiring dialysis or eGFR <30 L/min/1.73m2 calculated using 2021 CKD-EPI equation described in Section 10.8.2.1."}
• {"criterion_text":"-Left ventricular ejection fraction <50% on echocardiogram (or MUGA scan)."}
• {"criterion_text":"-Other Exclusion Criteria: Current adherence to a calorie-restricted diet with the intention of weight loss within 6 months prior to Screening/Visit 1"}
• {"criterion_text":"-Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members."}
• {"criterion_text":"-Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification."}
• {"criterion_text":"-Cachexia caused by reasons other than mPDAC, as determined by the investigator, including, but not limited to: •Severe COPD requiring use of home O2 •Active, uncontrolled or untreated AIDS"}
• {"criterion_text":"-Undergoing major surgery (central venous access placement, endoscopic retrograde cholangiopancreatography with or without biliary stent placement, and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Participants must have recovered from acute effects of surgery prior to screening. Participants should not have plans to undergo major surgical procedures during the study."}
• {"criterion_text":"-Clinically significant ascites that requires medical intervention or underwent a paracentesis within 4 weeks prior to randomization."}
• {"criterion_text":"-History of any secondary malignancy in the last 2 years, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ."}
• {"criterion_text":"-Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study."}
• {"criterion_text":"-History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody."}
• {"criterion_text":"-Participants who have a history of allergy or hypersensitivity to any of the chemotherapeutics or any of their excipients, or participants who exhibit any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the chemotherapeutic prescribing Information."}
• {"criterion_text":"-Current or chronic HBV or HCV infection as evidenced by HBsAg and anti-hepatitis C antibody positivity, respectively, or known seropositivity for HIV."}

Primary endpoints

• {"endpoint_text":"-Percent change from baseline in body weight at Week 12.","definition_or_measurement_approach":"Percent change from baseline in body weight measured at Week 12."}
• {"endpoint_text":"-Change from baseline in FAACT-5IASS subscale scores at Week 12.","definition_or_measurement_approach":"Change from baseline in FAACT-5IASS subscale scores assessed at Week 12."}
• {"endpoint_text":"-Percent change from baseline body weight, in the open-label extension.","definition_or_measurement_approach":"Percent change from baseline in body weight measured during the open-label extension (OLE)."}

Secondary endpoints

• {"endpoint_text":"-Change from baseline at Week 12 in physical activity as measured by time spent in non-sedentary activity","definition_or_measurement_approach":"Physical activity measured by wearable DHT watch; time spent in non-sedentary activity at Week 12."}
• {"endpoint_text":"-Overall survival, defined as the time from randomization to occurrence of all-cause death","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"-Change from baseline in body weight (kg) at Week 12","definition_or_measurement_approach":"Absolute change in body weight in kilograms measured at Week 12."}
• {"endpoint_text":"-Change from baseline at Week 12 in physical activity as measured by total vector magnitude","definition_or_measurement_approach":"Physical activity measured by wearable DHT watch; total vector magnitude at Week 12."}
• {"endpoint_text":"-PFS, as determined by BICR assessment per RECIST 1.1","definition_or_measurement_approach":"Progression-free survival determined by Blinded Independent Central Review (BICR) using RECIST 1.1."}
• {"endpoint_text":"-ORR, as determined by BICR assessment per RECIST 1.1","definition_or_measurement_approach":"Objective response rate determined by BICR per RECIST 1.1."}
• {"endpoint_text":"-DCR, as determined by BICR assessment per RECIST 1.1","definition_or_measurement_approach":"Disease control rate determined by BICR per RECIST 1.1."}
• {"endpoint_text":"-DOR, as determined by BICR assessment per RECIST 1.1","definition_or_measurement_approach":"Duration of response determined by BICR per RECIST 1.1."}
• {"endpoint_text":"-Change from baseline in body composition as measured by CT scan at Week 12 and and all other collected time points. CT (or MRI) based measures will include: •LSMI •Skeletal muscle area and radiodensity at third lumbar vertebra (L3) •Intermuscular adipose area and radiodensity at L3 •Subcutaneous adipose area and radiodensity at L3 •Visceral adipose area and radiodensity at L3","definition_or_measurement_approach":"CT (or MRI) measures including LSMI, skeletal muscle area and radiodensity at L3, intermuscular adipose area and radiodensity at L3, subcutaneous and visceral adipose area and radiodensity at L3, assessed at Week 12 and other timepoints."}
• {"endpoint_text":"-Incidence of: •TEAEs •SAEs •AEs leading to permanent discontinuation from study intervention or study •Clinical laboratory abnormalities •Vital Sign abnormalities •ECG abnormalities","definition_or_measurement_approach":"Safety endpoints: incidence and severity of treatment-emergent adverse events (TEAEs), SAEs, AEs leading to permanent discontinuation, clinical laboratory, vital signs, and ECG abnormalities."}
• {"endpoint_text":"-Change from baseline at Week 12: •PROMIS®-Physical Function (version 8c, 7-day) •PROMIS®-Fatigue (version 7a)","definition_or_measurement_approach":"Patient-reported outcomes measured by PROMIS® Physical Function v8c (7-day) and PROMIS® Fatigue v7a at Week 12."}
• {"endpoint_text":"-Change from baseline at all collected time points: •Body weight (and percent change) •FAACT Total and Sub-scale Scores (including FAACT-5IASS) •Time spent in non-sedentary activity •\tTotal vector magnitude •PROMIS®-Physical Function (version 8c, 7-day) •PROMIS®-Fatigue (version 7a)","definition_or_measurement_approach":"Longitudinal assessments of body weight, FAACT total and subscales (including FAACT-5IASS), wearable-derived activity measures, PROMIS physical function and fatigue at all collected time points."}
• {"endpoint_text":"-Occurrence and severity of the symptomatic AEs including diarrhea, nausea, vomiting, decreased appetite, fatigue, and mouth sores by maximum grade as assessed by the NCI PRO CTCAE. •Overall side-effect impact as assessed by FACIT-GP5","definition_or_measurement_approach":"Symptomatic AEs graded by NCI PRO-CTCAE; overall side-effect impact assessed by FACIT-GP5."}
• {"endpoint_text":"-Occurrence of chemotherapy dosing changes (including dose reductions, dosing interruptions, and permanent treatment discontinuations) due to occurrence of the AEs of nausea, vomiting, diarrhea, appetite decreased, or fatigue","definition_or_measurement_approach":"Recording of chemotherapy dosing modifications (dose reductions, interruptions, discontinuations) attributable to specific AEs."}
• {"endpoint_text":"-Tumor status as determined by BICR assessment per RECIST 1.1 using CT scan (or MRI) at Week 12 and all other collected time points","definition_or_measurement_approach":"Tumor assessments by BICR per RECIST 1.1 using CT (or MRI) at Week 12 and other timepoints."}
• {"endpoint_text":"-Change from baseline at Week 12 and all other collected time points on ECOG PS","definition_or_measurement_approach":"Change in ECOG performance status from baseline at Week 12 and other collected time points."}
• {"endpoint_text":"-OLE: Incidence of: •TEAEs •SAEs •AEs leading to permanent discontinuation from study intervention or study •Clinical laboratory test abnormalities •Vital Sign abnormalities","definition_or_measurement_approach":"Safety incidence measures during the open-label extension: TEAEs, SAEs, AEs leading to discontinuation, clinical laboratory and vital sign abnormalities."}

Methods

• Study Brochure (country- and language-specific study brochures available as recruitment material) - patient-facing informational brochure
• Cachexia flyer (country/language specific) - targeted print/digital flyer for patients with cachexia
• Image Board / Image materials - visual recruitment materials for sites
• Advocacy listing and media board - materials to engage patient advocacy groups and media channels
• Study visit guide - recruitment/visit information for participants
• ePRO / patient-facing electronic materials - electronic patient-reported outcome materials (D4_Patient facing material_ePRO)

Belgium

Earliest CTIS Part Ii Submission Date

28-11-2025

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

159

Number Of Sites

5

Number Of Participants

22

Bulgaria

Earliest CTIS Part Ii Submission Date

28-11-2025

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

164

Number Of Sites

4

Number Of Participants

33

France

Earliest CTIS Part Ii Submission Date

18-11-2025

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

174

Number Of Sites

6

Number Of Participants

60

Germany

Earliest CTIS Part Ii Submission Date

26-11-2025

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

161

Number Of Sites

7

Number Of Participants

28

Italy

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

196

Number Of Sites

5

Number Of Participants

26

Poland

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

157

Number Of Sites

6

Number Of Participants

34

Slovakia

Earliest CTIS Part Ii Submission Date

27-11-2025

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

159

Number Of Sites

7

Number Of Participants

34

Spain

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

157

Number Of Sites

9

Number Of Participants

52

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Premier Research International LLC

Responsibilities

Dictionary Coding

Name

Icon Clinical Research Limited

Responsibilities

Medical Imaging - Central Reader/Reading Service

Name

Signant Health Global Solutions Limited

Responsibilities

Electronic COA (eCOA) Support Services

Name

Q Squared Solutions LLC

Responsibilities

Biospecimen testing

Name

Labcorp Central Laboratory Services LP

Responsibilities

Central laboratory services

Third parties

• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Biospecimen testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"Dictionary Coding","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central laboratory services (clinical labs)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Signant Health Global Solutions Limited","duties_or_roles":"Electronic COA (eCOA) Support Services","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Medical Imaging - Central Reader/Reading Service","organisation_type":"Pharmaceutical company"}