Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15 (PROACC-1)

A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF PONSEGROMAB IN PATIENTS WITH CANCER, CACHEXIA, AND ELEVATED CONCENTRATIONS OF GDF-15, FOLLOWED BY AN OPTIONAL OPEN-LABEL TREATMENT PERIOD (PROACC -1)

Study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15.

Study Overview

• Status: Completed
• Conditions: Fatigue; Colorectal Cancer; Pancreatic Cancer; Cachexia; Non-small Cell Lung Cancer; Loss of Appetite
• Intervention / Treatment: Drug: ponsegromab; Drug: Placebo for ponsegromab

Detailed Description

A 12 week double blind study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15.

During the initial 12-week treatment period (Part A), a total of 3 doses of ponsegromab or placebo will be administered 4 weeks apart subcutaneously. Each dose contains two injections. Part B is an optional open-label treatment period consisting of ponsegromab administered every 4 weeks subcutaneously for up to one year. Part B does not include placebo.

Assessments include:

• Body weight measurements
• Measure the impact of ponsegromab compared to placebo on physical activity.
• Measure the impact of ponsegromab compared to placebo on appetite, fatigue, nausea, vomiting and physical function questionnaires.
• Blood samples to evaluate safety and additional endpoints including the amount of study drug in the blood and the effects of the study drug on levels of GDF15
• Up to 3 additional blood samples (two samples during Part A and one sample during Part B, if relevant) in a subset of participants as part of a substudy for more comprehensive assessment of the amount of study drug in the blood and of the effects of the study drug on levels of GDF-15.

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Orange, New South Wales, Australia, 2800
      • Orange Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
    • St Albans, Victoria, Australia, 3021
      • Western Health-Sunshine & Footscray Hospitals
• Bulgaria
  • Burgas, Bulgaria, 8000
    • Complex Oncology Center - Burgas
  • Haskovo, Bulgaria, 6300
    • Specialized Hospital for Active Treatment of Oncology - Haskovo
  • Ruse, Bulgaria, 7002
    • Complex Oncology Center - Ruse EOOD
  • Shumen, Bulgaria, 9700
    • Complex Oncology Center - Shumen
  • Sofia, Bulgaria, 1797
    • University Multiprofile Hospital for Active Treatment Sofiamed
  • Sofia, Bulgaria, 1303
    • Multiprofile Hospital for Active Treatment Serdika EOOD
  • Sofia, Bulgaria, 1330
    • MHAT for Women's Health Nadezhda
  • Vratsa, Bulgaria, 3000
    • Complex Oncology Center - Vratsa
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • CIUSSS- saguenay-Lac-Saint-Jean
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Changhai Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provincial Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China, 325035
      • The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1121
    • Orszagos Koranyi Pulmonologiai Intezet
  • Bács-kiskun
    • Kecskemét, Bács-kiskun, Hungary, 6000
      • Bács-Kiskun Vármegyei Oktatókórház
  • Jász-nagykun-szolnok
    • Szolnok, Jász-nagykun-szolnok, Hungary, 5004
      • Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz
• Japan
  • Kyoto, Japan, 602-8566
    • University Hospital,Kyoto Prefectural University of Medicine
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital Of JFCR
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
  • Nagoya, Aichi
    • Nagoya, Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Shizuoka
    • Nagaizumi-cho, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
• Poland
  • Grudziadz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. Dr. Wladyslawa Bieganskiego
  • Katowice, Poland, 40-060
    • NZOZ "Vegamed"
  • Lublin, Poland, 20-093
    • Specjalistyczna Praktyka Lekarska Slawomir Mandziuk
  • Małopolskie
    • Kraków, Małopolskie, Poland, 30-348
      • Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica
  • Bratislava, Slovakia, 826 06
    • Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
  • Bratislava, Slovakia, 833 10
    • Narodny onkologicky ustav, II. Onkologicka klinika LFUK a NOU
  • Nove Zamky, Slovakia, 940 34
    • Fakultna nemocnica s poliklinikou Nove Zamky
  • Partizanske, Slovakia, 95801
    • Nemocnica na okraji mesta, n.o.
  • Trnava, Slovakia, 917 75
    • Fakultna Nemocnica Trnava
• Spain
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • València, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona [barcelona]
    • Sant Cugat del Vallès, Barcelona [barcelona], Spain, 08915
      • Hospital Universitari General de Catalunya
  • Catalunya [cataluña]
    • L'Hospitalet de Llobregat, Catalunya [cataluña], Spain, 08908
      • Institut Catala d'Oncologia - L'Hospitalet
  • Illes Balears [islas Baleares]
    • Palma, Illes Balears [islas Baleares], Spain, 07198
      • Hospital Son Llatzer
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46009
      • Fundacion Instituto Valenciano de Oncologia
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 404332
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
  • Tainan
    • Tainan City, Tainan, Taiwan, 73657
      • Chi Mei Hospital - Liouying Branch
• United States
  • Arkansas
    • Conway, Arkansas, United States, 72034
      • CARTI Conway
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
    • North Little Rock, Arkansas, United States, 72117
      • CARTI North Little Rock
    • Stuttgart, Arkansas, United States, 72160
      • CARTI Stuttgart
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center INC
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Redlands, California, United States, 92373
      • Emad Ibrahim,MD,INC.
    • Santa Rosa, California, United States, 95403
      • Providence Medical Foundation
  • Indiana
    • Lafayette, Indiana, United States, 47904
      • IU Health Arnett Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Health Deaconess Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University: Center for Health and Healing 1
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University: Center for Health and Healing 2
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78212
      • Carta - Clinical Associates in Research Therapeutics of America, LLC
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Documented active diagnosis of non-small cell lung, pancreatic, colorectal cancer
• Cachexia defined by Fearon criteria of weight loss
• Serum GDF-15 concentrations
• Signed informed consent
• ECOG PS ≤3 with life expectancy of at least 4 months to be able to complete Part A.

Key Exclusion Criteria:

• Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization.
• Current active reversible causes of decreased food intake.
• Cachexia caused by other reasons.
• History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody.
• inadequate liver function
• renal disease requiring dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment; ponsegromab low dose subcutaneous injection every 4 weeks	Drug: ponsegromab; Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment
Placebo Comparator: Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment; Match placebo subcutaneous injection every 4 weeks	Drug: Placebo for ponsegromab; Double-Blind placebo Treatment followed by Open Label ponsegromab Treatment
Experimental: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment; ponsegromab medium dose subcutaneous injection every 4 weeks	Drug: ponsegromab; Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment
Experimental: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment; ponsegromab high dose subcutaneous injection every 4 weeks	Drug: ponsegromab; Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change From Baseline in Body Weight at Week 12	Body weight was measured in kilograms using a calibrated weighing scale. Baseline was defined as the last average of the duplicate measurements prior to, or on Day 1. The average of the duplicate body weights collected at assessment time was considered. The posterior medians and 90 percent (%) credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for each randomized dose (including placebo). 4-Parameter maximal effect (E max) model: change from baseline = E 0 + (E max * dose^Hill) / (ED 50^Hill + dose^Hill), where E0 is the placebo effect, E max is the maximum effect, ED 50 is the dose producing 50% of the maximum effect, and Hill is the slope parameter. Model utilized a Bayesian methodology with a robustified, informative meta-analytic predictive prior for the placebo change from baseline at week 12.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change From Baseline in Physical Activity at Week 12	Physical activity was monitored using accelerometry (wearable digital sensors). Physical activity was categorized as: sedentary activity, non-sedentary physical activity, and moderate to vigorous physical activity. In this outcome measure time for each type of physical activity per day was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using mixed models repeated measures (MMRM) model.	Baseline, Week 12
Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12	Physical activity was monitored using accelerometry (wearable digital sensors). In this outcome measure mean activity level during maximum 6 minutes was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.	Baseline, Week 12
Part A: Change From Baseline in Total Vector Magnitude at Week 12	Total vector magnitude is a measure of overall physical activity. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.	Baseline, Week 12
Part A: Change From Baseline in Gait at Week 12	Gait was monitored using accelerometry (wearable digital sensors). Analysis was performed using MMRM model. Gait included: gait speed and 95th percentile of gait speed. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.	Baseline, Week 12
Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12	FAACT-ACS is a 12-item symptom-specific subscale to measure participants' concerns about their anorexia (appetite) or cachexia (weight) for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-ACS score ranged from 0 to 48. Higher scores are associated with a higher health-related quality of life. FAACT-ACS was analyzed using an MMRM model.	Baseline (prior to dose on Day 1), Week 12
Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12	FAACT-5IASS is a 5-item subscale to measure participants' perceptions of anorexia (appetite) concerns for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-5IASS score ranged from 0 to 20. Higher scores are associated with a higher health-related quality of life. FAACT-5IASS was analyzed using an MMRM model.	Baseline (prior to dose on Day 1), Week 12
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue	The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue. Participants rated appetite, nausea and physical fatigue symptom every day, and weekly averages were calculated over the 7 days prior, from 0 to 10, where 0 = no symptom and 10 = worst possible symptom. Higher scores indicated more severe disease. CRCSD was analyzed using an MMRM model.	Baseline, Week 12
Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency	The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: vomiting frequency. Participants rated vomiting frequency over the past 24 hours, from 0 to 30, where 0 = no symptom and 30 = worst possible symptom. Higher scores indicated more severe disease.	Baseline, Week 12
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE)	An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE were defined as any event that was not present before exposure to study drug, or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included serious AEs and all non-SAEs.	From start of study drug on Day 1 maximum up to 4 weeks post last dose on Week 12 (maximum up to approximately Week 16)
Part A: Number of Participants With Incidence of Laboratory Test Abnormalities	Laboratory test abnormality parameters included: hematology- hemoglobin (gram per deciliter [g/dL]), hematocrit (%), erythrocytes (10^12/Liter [L]) less than (<) 0.8*lower limit of normal (LLN); platelets (10^9/L) <0.5*LLN to more than (>) 1.75*upper limit of normal (ULN); leukocytes (10^9/L) <0.6*LLN to >1.5*ULN; lymphocytes, neutrophils (10^9/L) <0.8*LLN to >1.2*ULN. Clinical chemistry- bilirubin, glucose (mg/dL) >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (Units/L [U/L]) >3.0*ULN; protein, albumin (gram [g]/dL) <0.8*LLN; urea (mmol/L) >1.3xULN; creatinine (mg/dL) >1.3*ULN; sodium (milliequivalents [mEq]/L) <0.95*LLN; potassium (mEq/L) <0.9*LLN to >1.1*ULN.	Day 1 up to Week 12
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria	Vital signs criteria included: supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg), increase and decrease in change of more than or equal to (>=) 30mmHg; supine diastolic blood pressure (DBP) <50 mmHg, increase and decrease in change of >= 20mmHg; pulse rate <40 beats per minute (bpm) to >120 bpm. Only rows which included at least 1 participant in any reporting group with abnormality were reported in this outcome measure.	Day 1 up to Week 12
Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities	ECG parameters included heart rate (HR), PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. HR: RR (interval between 2 successive R waves on ECG) decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100, RR increase >25% and to a VR <50; PR interval: baseline less than or equal to (<=) 200 and % change >= 50%; QT interval: >450, >480, >500, increase from baseline >30, increase from baseline >60; QTcF: 470 < value <= 480, 480 < value <= 500, value > 500, 30 < change <= 60 and change >60; QRS complex: value >= 140, % change >=50%. Clinically significant values were determined by the investigator.	Day 1 up to Week 12

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Actual): March 13, 2024
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: August 12, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: fatigue; cancer; weight loss; cachexia; anorexia; loss of appetite
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Body Weight; Signs and Symptoms, Digestive; Body Weight Changes; Weight Loss; Thinness; Fatigue; Anorexia; Wasting Syndrome; Cachexia
• Other Study ID Numbers: C3651003; 2023-510446-24-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No