Trial Outcomes & Findings for Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15 (NCT NCT05546476)

A total of 187 participants were enrolled in this study. This study had 2 parts: Part A and Part B. On completion of Part A, participants had the opportunity to enter open-label extension period Part B (optional).

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.