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RecruitingLast updated: 9 February 2026

RIVER-mPDAC: Evaluating whether adding a targeted medicine to standard chemotherapy improves outcomes for people with metastatic pancreatic cancer and severe weight and muscle loss caused by cancer (cachexia)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

Trial purpose

Medical clipboardCancer treatment; Side effect and wellbeing

Tumor type

Upper gastrointestinal tract Cancers Upper gastrointestinal tract

Age

People18+

Trial acronym

RIVER-mPDAC

Clinical summary

Summary

This study is for adults who have metastatic pancreatic cancer (mPDAC) and are also experiencing cachexia, which is severe weight and muscle loss caused by cancer. The study is testing whether a medicine called ponsegromab, given together with standard chemotherapy, can improve outcomes compared with chemotherapy alone.

Everyone in the study will receive standard chemotherapy. The two chemotherapy options are:

  • nab-paclitaxel + gemcitabine, or
  • FOLFIRINOX (or mFOLFIRINOX)

Before starting the study medicine, participants need to complete 1 cycle of nab-paclitaxel + gemcitabine, or 2 cycles of FOLFIRINIX. 

People will then be randomly assigned (by chance) to receive either ponsegromab or a placebo. This will be taken on the same day as the next chemotherapy cycle, and before chemotherapy is given.

The study has two main parts: Phase 2b and Phase 3.

Phase 2b
Participants are randomly assigned to one of three groups:

  • Ponsegromab (dose 1) + chemotherapy
  • Ponsegromab (dose 2) + chemotherapy
  • Placebo + chemotherapy

After 12 weeks, researchers will decide which dose works best.

Phase 3
Only the selected dose of ponsegromab will continue into Phase 3. Participants will be randomly assigned to either:

  • The selected ponsegromab dose + chemotherapy
  • Placebo + chemotherapy

During Phase 3, caregivers can join an optional sub-study to see whether ponsegromab also helps reduce caregiver burden and improve their wellbeing.

Conditions

This trial is treating people with cachexia and metastatic pancreatic ductal adenocarcinoma

Eligibility

Inclusion

  • 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

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had a certain type of treatment or surgical procedure.
  • You have the type of cancer, symptoms, or health risks that this clinical trial is focused on.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

Trial sponsor

Pfizer

Scientific 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

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