Evidence map›Paper›PMID 36634920›Full record

ArticleJournal for immunotherapy of cancer2023

Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.

Charlotte Lemech, Keith Dredge, Darryn Bampton, Edward Hammond, Andrew Clouston, Nigel J Waterhouse, Amanda C Stanley, Lucie Leveque-El Mouttie, Grace M Chojnowski, Andrew Haydon and 4 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05061017 (Phase IIA Basket Study of Pixatimod), which is not on this map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05061017 phase2completednot on this map

Phase IIA Basket Study of Pixatimod (PG545) in Combination With Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and Pixatimod (PG545) in Combination With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC)

TypeinterventionalSponsorDiwakar DavarRan2021 to 2024Enrolled13ConditionsNSCLC, Metastatic Colorectal Carcinoma, Refractory MelanomaArmsPixatimod, Nivolumab, Cyclophosphamide (low dose)
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Advancing Immunotherapy in Pancreatic Cancer.International journal of molecular sciences · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 4 countries.

Charlotte LemechScientia Clinical Research Ltd, Sydney, New South Wales, Australia.
Keith DredgeZucero Therapeutics Ltd, Brisbane, Queensland, Australia keith.dredge@zucero.com.au.
Darryn BamptonZucero Therapeutics Ltd, Brisbane, Queensland, Australia.
Edward HammondZucero Therapeutics Ltd, Brisbane, Queensland, Australia.ORCID 0000-0001-7405-8684
Andrew CloustonDepartment of Pathology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Nigel J WaterhouseQIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Amanda C StanleyQIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Lucie Leveque-El MouttieQIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Grace M ChojnowskiQIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Andrew HaydonMedical Oncology, The Alfred Hospital, Melbourne, Victoria, Australia.
Nick PavlakisMedical Oncology, Genesis Care, North Shore Health Hub, St Leonards, New South Wales, Australia.
Matthew BurgeMedical Oncology, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Michael P BrownCancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.ORCID 0000-0002-5796-1932
David GoldsteinMedical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
QIMR Berghofer Medical Research Institute · AURoyal Brisbane and Women's Hospital · AUPrince of Wales Hospital · AUSouth Australia Pathology · AUThe Alfred Hospital · AUThe University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPixatimod is a unique activator of the Toll-like Receptor 9 pathway. This phase I trial evaluated safety, efficacy and pharmacodynamics of pixatimod and PD-1 inhibitor nivolumab in immunologically cold cancers.

methods3+3 dose escalation with microsatellite stable metastatic colorectal cancer (MSS mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC) expansion cohorts. Participants received pixatimod once weekly as a 1-hour intravenous infusion plus nivolumab every 2 weeks. Objectives included assessment of safety, antitumor activity, pharmacodynamics, and pharmacokinetic profile.

resultsFifty-eight participants started treatment. The maximum tolerated dose of pixatimod was 25 mg in combination with 240 mg nivolumab, which was used in the expansion phases of the study. Twenty-one grade 3-5 treatment-related adverse events were reported in 12 participants (21%); one participant receiving 50 mg pixatimod/nivolumab had a treatment-related grade 5 AE. The grade 3/4 rate in the MSS mCRC cohort (n=33) was 12%. There were no responders in the mPDAC cohort (n=18). In the MSS mCRC cohort, 25 participants were evaluable (initial postbaseline assessment scans >6 weeks); of these, three participants had confirmed partial responses (PR) and eight had stable disease (SD) for at least 9 weeks. Clinical benefit (PR+SD) was associated with lower Pan-Immune-Inflammation Value and plasma IL-6 but increased IP-10 and IP-10/IL-8 ratio. In an MSS mCRC participant with PR as best response, increased infiltration of T cells, dendritic cells, and to a lesser extent NK cells, were evident 5 weeks post-treatment.

conclusionsPixatimod is well tolerated at 25 mg in combination with nivolumab. The efficacy signal and pharmacodynamic changes in MSS mCRC warrants further investigation. TRIAL REGISTRATION NUMBER: NCT05061017.

Indexed as

AdenocarcinomaColorectal NeoplasmsAngiogenesis InhibitorsChemokine CXCL10HumansMicrosatellite RepeatsNivolumabPancreatic NeoplasmsToll-Like Receptor 9Angiogenesis InhibitorsChemokine CXCL10NivolumabTLR9 protein, humanToll-Like Receptor 9Drug Therapy, CombinationImmunomodulationImmunotherapyLymphocyte Activation

Identifiers

PMID36634920
PMCPMC9843174
OpenAlexW4315780755

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.