Recruiting 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

Phase II / Phase III Interventional Cachexia Metastatic Pancreatic Ductal Adenocarcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: ponsegromab, placebo.
Who it may be relevant to: Registry conditions: Cachexia, Metastatic Pancreatic Ductal Adenocarcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Belgium, Brazil, Bulgaria +16
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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 their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-days cycles of FOLFIRINOX) 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 start their next cycle 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 their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-day cycles of FOLFIRINOX) 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 start their next cycle 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:

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 their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-days cycles of FOLFIRINOX) 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 start their next cycle 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 extension where they will receive ponsegromab for up to 12 months.

Interventions

Drug ponsegromab
Double-Blind ponsegromab Treatment
Drug placebo
Double-Blind placebo Treatment

Primary outcome measures

Percent change from baseline in body weight for ponsegromab compared to placebo [Time frame: Baseline, Week 12]
Change from baseline in Functional Assessment of Anorexia/Cachexia Therapy 5-item Anorexia Symptom Scale scores [Time frame: Baseline, Week 12]

Secondary outcome measures (12)

Change from baseline in non-sedentary physical activity time [Time frame: Baseline, Week 12]
Overall survival [Time frame: Randomization through completion of Phase 3 of the study, an average of 1 year]
Change from baseline in body weight (kg) [Time frame: Baseline, Week 12 and up to Week 52]
Change from baseline at Week 12 in physical activity as measured by total vector magnitude [Time frame: Baseline, Week 12]
Effect on progression free survival [Time frame: Randomization through completion of Phase 3 of the study, an average of 1 year]
Effect on objective response rate [Time frame: Baseline, Week 52]
Effect on disease control rate [Time frame: Baseline, Week 52]
Effect on duration of response [Time frame: Baseline, Week 52]
Change from baseline in skeletal muscle area and radiodensity at third lumbar vertebra (L3) [Time frame: Baseline, Week 12]
Change from baseline in intermuscular adipose area and radiodensity at L3 [Time frame: Baseline, Week 12]
Change from baseline in subcutaneous adipose area and radiodensity at L3 [Time frame: Baseline, Week 12]
Change from baseline in visceral adipose area and radiodensity at L3 [Time frame: Baseline, Week 12]

Eligibility criteria

Inclusion criteria

Signed Informed Consent Document
Documented active diagnosis of metastatic pancreatic ductal adenocarcinoma
Cachexia defined by Fearon criteria of weight loss
Completed 1 x 28-day cycle of first-line systemic nab-paclitaxel and gemcitabine chemotherapy or 2 x 14-day cycles of FOLFIRINOX chemotherapy and prior to receiving Cycle 2 chemotherapy
ECOG PS ≤1 with life expectancy of at least 4 months

Exclusion criteria

Current active reversible causes of decreased food intake
Cachexia caused by other reasons
Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification
Left ventricular ejection fraction <50%
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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment