2025-522093-36-00招募中3 期
C3651021: A PHASE 2b/3, RANDOMIZED, DOUBLE-BLIND STUDY TO INVESTIGATE THE EFFICACY, SAFETY, AND TOLERABILITY OF PONSEGROMAB (PF-06946860) COMPARED WITH PLACEBO BOTH WITH BACKGROUND FIRST-LINE CHEMOTHERAPY IN ADULT PARTICIPANTS WITH CACHEXIA AND METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 56
- 试验地点
- 12
- 主要终点
- Percent change from baseline in body weight at Week 12.
研究概览
简要总结
- To evaluate the effect of ponsegromab compared with placebo on body weight.
- To evaluate the effect of ponsegromab compared with placebo on the appetiterelated symptoms as measured by FAACT-5IASS
- Primary (OLE): To evaluate the effect of ponsegromab on body weight
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Aged ≥18 years of age (or the minimum age of consent in accordance with local regulations if >18 years) at the Screening Visit.
- •Documented histologic or cytologic active diagnosis of mPDAC (locally advanced disease is not eligible) • Measurable 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.
- •and: • Completed 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.
- •Cachexia as defined by Fearon criteria (see Section 8.1.1 for details on documented body weight from medical records): • BMI < 20 kg/m2 and involuntary weight loss of > 2% within 6 months prior to screening • Involuntary weight loss of >5% over the past 6 months prior to screening irrespective of BMI
- •Participants who are assessed by the investigator to have: • an ECOG PS ≤1 and • a life expectancy of ≥4 months.
排除标准
- •Medical Conditions: Current active reversible causes of decreased food intake, as determined by the investigator. These causes may include, but are not limited to: • NCI CTCAE Grade 3 or 4 oral mucositis • NCI CTCAE Grade 3 or 4 GI disorders (nausea, vomiting, diarrhea, and constipation) • Mechanical obstructions interfering with the participant's ability to eat
- •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.
- •Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
- •Symptomatic brain metastasis or leptomeningeal disease.
- •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.
- •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.
- •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.
- •Previous participation in a clinical study evaluating ponsegromab (including exposure to placebo).
- •Diagnostic Assessments: Renal disease requiring dialysis or eGFR <30 mL/min/1.73m2 calculated using 2021 CKD-EPI equation described in Section 10.8.2.
- •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: • Total bilirubin ≥1.5 × ULN (For Gilbert’s syndrome, direct bilirubin >ULN is exclusionary) • AST 3 × ULN (AST 5× ULN if there is liver involvement by the tumor) • ALT 3 × ULN (ALT 5× ULN if there is liver involvement by the tumor) • Alkaline 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).
- •Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >470 ms).
- •Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
- •Left ventricular ejection fraction <50% on echocardiogram (or MUGA scan).
- •Other Exclusion Criteria: Current adherence to a calorie-restricted diet with the intention of weight loss within 6 months prior to Screening/Visit 1
- •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.
- •Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification.
- •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
- •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.
- •Clinically significant ascites that requires medical intervention or underwent a paracentesis within 4 weeks prior to randomization.
- •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.
- •History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody.
- •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.
结局指标
主要结局
Percent change from baseline in body weight at Week 12.
Percent change from baseline in body weight at Week 12.
Change from baseline in FAACT-5IASS subscale scores at Week 12.
Change from baseline in FAACT-5IASS subscale scores at Week 12.
Percent change from baseline body weight, in the open-label extension.
Percent change from baseline body weight, in the open-label extension.
次要结局
- Change from baseline at Week 12 in physical activity as measured by time spent in non-sedentary activity
- Overall survival, defined as the time from randomization to occurrence of all-cause death
- Change from baseline in body weight (kg) at Week 12
- Change from baseline at Week 12 in physical activity as measured by total vector magnitude
- PFS, as determined by BICR assessment per RECIST 1.1
- ORR, as determined by BICR assessment per RECIST 1.1
- DCR, as determined by BICR assessment per RECIST 1.1
- DOR, as determined by BICR assessment per RECIST 1.1
- 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
- Incidence of: •TEAEs •SAEs •AEs leading to permanent discontinuation from study intervention or study •Clinical laboratory abnormalities •Vital Sign abnormalities •ECG abnormalities
- Change from baseline at Week 12: •PROMIS®-Physical Function (version 8c, 7-day) •PROMIS®-Fatigue (version 7a)
- 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 • Total vector magnitude •PROMIS®-Physical Function (version 8c, 7-day) •PROMIS®-Fatigue (version 7a)
- 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
- 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
- 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
- Change from baseline at Week 12 and all other collected time points on ECOG PS
- OLE: Incidence of: •TEAEs •SAEs •AEs leading to permanent discontinuation from study intervention or study •Clinical laboratory test abnormalities •Vital Sign abnormalities
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (12)
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