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

Pfizer

Status and phase: Begins enrollment in 2 months; Phase 3; Phase 2

Conditions: Metastatic Pancreatic Ductal Adenocarcinoma; Cachexia

Treatments: Drug: placebo; Drug: ponsegromab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06989437

C3651021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 982 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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982 participants in 3 patient groups, including a placebo group

Double-Blind ponsegromab Treatment lower dose

Experimental group

Description:

ponsegromab 200 mg subcutaneous injection every 4 weeks

Treatment:

Drug: ponsegromab

Double-Blind ponsegromab Treatment higher dose

Experimental group

Description:

ponsegromab 400 mg subcutaneous injection every 4 weeks

Treatment:

Drug: ponsegromab

Double-Blind Placebo Treatment

Placebo Comparator group

Description:

Match placebo subcutaneous injection every 4 weeks

Treatment:

Drug: placebo