# Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma

Source: https://onco.cc/key-papers/paper-halo-301-pegvorhyaluronidase-jco-2020/  
OnCo record `paper-halo-301-pegvorhyaluronidase-jco-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The 2020 trial of an enzyme meant to dissolve the dense matrix around pancreatic tumours so chemotherapy could reach them: more tumours shrank, but patients lived no longer, and the drug was abandoned.

## Summary

HALO 109-301 was a phase 3, randomised, double-blind, placebo-controlled trial in untreated, metastatic, hyaluronan-high pancreatic ductal adenocarcinoma. Patients were randomised 2:1 to pegvorhyaluronidase alfa (PEGPH20, 3.0 micrograms per kilogram twice weekly in cycle 1 then weekly) plus nab-paclitaxel and gemcitabine, or placebo plus the same chemotherapy; 494 were randomised and 492 analysed (327 versus 165). With 330 deaths, median overall survival was 11.2 versus 11.5 months (hazard ratio 1.00, 95 percent confidence interval 0.80 to 1.27, P = 0.97); median progression-free survival 7.1 versus 7.1 months; objective response 47 versus 36 percent. Grade 3 or higher fatigue (16.0 versus 9.6 percent), muscle spasms (6.5 versus 0.6) and hyponatraemia (8.0 versus 3.8) were commoner with PEGPH20. The authors concluded the results do not support further development.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: pancreatic-evidence
- Journal: Journal of Clinical Oncology
- Year: 2020
- DOI: 10.1200/JCO.20.00590
- Authors: Van Cutsem E, Tempero MA, Sigal D, et al.
- Findings: 492 patients analysed, hyaluronan-high, 2:1 randomisation, double-blind.; Median overall survival 11.2 versus 11.5 months (hazard ratio 1.00); progression-free survival 7.1 versus 7.1 months.; Objective response 47 versus 36 percent.; More grade 3 or higher fatigue, muscle spasms and hyponatraemia with PEGPH20.
- What it means: The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.
- Caveats: Hyaluronan-high selection by a companion assay; the result does not exclude other stromal targets.; Response rate rose without survival, a pattern seen again with other pancreatic agents.

## Sources

- J Clin Oncol 2020: https://doi.org/10.1200/JCO.20.00590
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32706635/
- ClinicalTrials.gov NCT02715804: https://clinicaltrials.gov/study/NCT02715804
- Trial design rationale (Future Oncol 2018): https://doi.org/10.2217/fon-2017-0338

## Connected records

- key papers: [Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival](https://onco.cc/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/), [MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer](https://onco.cc/key-papers/paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013/), [Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma](https://onco.cc/key-papers/paper-van-cutsem-j-clin-oncol/)
- cancers: [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/), [Stroma-rich and desmoplastic tumours in molecular data](https://onco.cc/terms/desmoplastic-stroma-rich/)
- people: [Eric Van Cutsem](https://onco.cc/people/eric-van-cutsem/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- ideas: [Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint](https://onco.cc/ideas/idea-pdac-stromal-reprogramming-not-depletion/)

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