Clinical trial NCT06989437: A Study to Learn About the Medicine Ponsegromab in Adults With Cancer of the Pancreas Which Has Spread and Caused Significant Body Weight Loss and Fatigue
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Cachexia
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: pancreatic cancer
metastatic cancer
cancer
anorexia
cachexia
weight loss
loss of appetite
fatigue
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2025-05-25
Enrollment: 982
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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 Cycle 1 of their first-line systemic chemotherapy 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 receive Cycle 2, Day 1 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 Cycle 1 of their first-line systemic chemotherapy 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 receive Cycle 2, Day 1 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:

* Continue the ponsegromab dose selected for Phase 3 if already randomized to that dose, OR
* Be switched to the ponsegromab dose selected for Phase 3 if randomized to the non-selected ponsegromab dose, OR
* Continue receiving placebo if randomized to placebo
* Remain blinded to study treatment

After the ponsegromab dose has been selected, continuing Phase 3 participants will:

* Continue the ponsegromab dose selected for Phase 3 if already randomized to that dose, OR
* Be switched to the ponsegromab dose selected for Phase 3 if randomized to the non-selected ponsegromab dose, OR
* Continue receiving placebo if randomized to placebo
* Remain blinded to study treatment Phase 3 participants enrolled after dose selection will be randomized 1:1 (ponsegromab selected dose: placebo). Participants must have completed Cycle 1 of their first-line systemic chemotherapy prior to the start of receiving their first dose (Day 1) of study intervention (selected Phase 3 ponsegromab dose or placebo). Day 1 study intervention must be taken on the same day participants receive Cycle 2, Day 1 of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy.

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 extention where they will receive ponsegromab for up to 12 months.

Eligibility criteria: Key inclusion Criteria:

* Signed Informed Consent Document
* Documented active diagnosis of metastatic pancreatic ductal adenocarcinoma
* Cachexia defined by Fearon criteria of weight loss
* Completed Cycle 1, first-line systemic chemotherapy and prior to receiving Cycle 2 chemotherapy
* ECOG PS ≤1 with life expectancy of at least 4 months

Key Exclusion Criteria:

* Current active reversible causes of decreased food intake
* Cachexia caused by other reasons
* Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization
* History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody
* History of allergy or hypersensitivity to any of the chemotherapeutics or any of their excipients
* Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma, symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases
* Inadequate liver function
* Renal disease requiring dialysis or eGFR \<30 mL/min/1.73m2

Primary outcomes:
measure: Percent change from baseline in body weight for ponsegromab compared to placebo
timeFrame: Baseline, Week 12
measure: Change from baseline in Functional Assessment of Anorexia/Cachexia Therapy 5-item Anorexia Symptom Scale scores
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change from baseline in non-sedentary physical activity time
timeFrame: Baseline, Week 12
measure: Overall survival
timeFrame: Randomization through completion of Phase 3 of the study, an average of 1 year
measure: Change from baseline in body weight (kg)
timeFrame: Baseline, Week 12 and up to Week 52
measure: Change from baseline at Week 12 in physical activity as measured by total vector magnitude
timeFrame: Baseline, Week 12
measure: Effect on progression free survival
timeFrame: Randomization through completion of Phase 3 of the study, an average of 1 year
measure: Effect on objective response rate
timeFrame: Baseline, Week 52
measure: Effect on disease control rate
timeFrame: Baseline, Week 52
measure: Effect on duration of response
timeFrame: Baseline, Week 52
measure: Change from baseline in skeletal muscle area and radiodensity at third lumbar vertebra (L3)
timeFrame: Baseline, Week 12
measure: Change from baseline in intermuscular adipose area and radiodensity at L3
timeFrame: Baseline, Week 12
measure: Change from baseline in subcutaneous adipose area and radiodensity at L3
timeFrame: Baseline, Week 12
measure: Change from baseline in visceral adipose area and radiodensity at L3
timeFrame: Baseline, Week 12
measure: 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.
timeFrame: Baseline, Week 12 and up to Week 52
measure: Number of participants with laboratory test abnormalities.
timeFrame: Baseline, Week 12 and up to Week 52
measure: Number of participants with vital signs abnormalities.
timeFrame: Baseline, Week 12 and up to Week 52
measure: Change in physical function, assessed on participant completed Patient-Reported Outcomes Measurement Information System Physical Function (version 8c) questionnaire.
timeFrame: Baseline, Week 12 and up to Week 52
measure: Change in fatigue, as assessed on participant completed Patient-Reported Outcomes Measurement Information System - Fatigue (version 7a) questionnaire.
timeFrame: Baseline, Week 12 and up to Week 52
measure: Occurrence of the TEAEs of nausea, vomiting, loss of appetite, or fatigue.
timeFrame: Baseline, Week 52
measure: Severity of the adverse events of nausea, vomiting, loss of appetite, or fatigue by maximum grade.
timeFrame: Baseline, Week 52
measure: Occurrence of chemotherapy dosing changes (including dosing reductions, dosing interruptions, and dosing discontinuations) due to occurrence of the TEAEs of nausea, vomiting, loss of appetite, or fatigue
timeFrame: Baseline, up to Week 52
measure: Tumor status
timeFrame: Baseline, Week 12 and up to Week 52
Other outcomes:
Locations:
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: