Phase Ib open-label, multicenter study of pixatimod - TLR9 activator in combination with nivolumab

Sep 24, 2026

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Pixatimod, a Toll-like receptor 9 pathway activator, was evaluated in a phase I study of safety, efficacy, and pharmacodynamics when combined with nivolumab in immunologically cold cancers. A 3+3 dose-escalation design enrolled microsatellite-stable metastatic colorectal cancer and metastatic pancreatic ductal adenocarcinoma expansion cohorts. Pixatimod was given weekly as a 1-hour infusion with nivolumab every 2 weeks. Fifty-eight participants started; the maximum tolerated dose was 25 mg with 240 mg nivolumab. In the MSS mCRC cohort, clinical benefit was linked to biomarker changes and partial responses/stable disease, warranting further study.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

Background

Methods

Results

Conclusions

What is already known on this topic

What this study adds

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Introduction

Open access Original research 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,1 Keith Dredge,2 Darryn Bampton,2 Edward Hammond 2 , Andrew Clouston,3 Nigel J Waterhouse,4 Amanda C Stanley,4 Lucie Leveque-El Mouttie,4 Grace M Chojnowski,4 Andrew Haydon,5 Nick Pavlakis,6,7 Matthew Burge,8 Michael P Brown ,9,10 David Goldstein11 To cite: Lemech C, Dredge K, Bampton D, et al. Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumabin subjects with microsatellitestable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors. Journal for ImmunoTherapy of Cancer 2023;11:e006136 . doi:10 . 1136/ jitc-2022-006136 ► Additional supplemental material is published online only. To view, please visit the journal online ([http://dx.doi.org/10](http://dx.doi.org/10) . 1136/jitc-2022-006136) . Accepted 14 December 2022 © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. For numbered affiliations see end of article. Correspondence to Dr Keith Dredge; [keith.dredge@zucero.com.au](keith.dredge@zucero.com.au) ABSTRACT Background Pixatimod is a unique activator of the Tolllike Receptor 9 pathway. This phase I trial evaluated safety, efficacy and pharmacodynamics of pixatimod and PD-1 inhibitor nivolumab in immunologically cold cancers. Methods 3+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. Results Fifty-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 MSSmCRC 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. Conclusions Pixatimod 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. WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Immunologically cold tumors, such as microsatellitestable metastatic colorectal cancer, contain limited numbers of tumor-targeting immune cells and have proven to be resistant to checkpoint inhibitor drugs such as anti-PD-1 agents.
WHAT THIS STUDY ADDS | | --- | | ⇒ This clinical trial evaluated a dendritic cell activating agent (pixatimod) in combination with the anti-PD-1 drug, nivolumab, to see whether this approach could demonstrate benefit to patients. The trial showed that the combination treatment was associated with manageable toxicity and signs of clinical benefit for colorectal patients and found evidence of biomarkers that correlate with clinical

FAQs

What was the main purpose of this phase Ib trial?

To evaluate the safety, efficacy, and pharmacodynamics of pixatimod combined with nivolumab in immunologically cold cancers, including MSS metastatic colorectal cancer and metastatic pancreatic ductal adenocarcinoma.

How were pixatimod and nivolumab administered?

Participants received pixatimod once weekly as a 1-hour intravenous infusion and nivolumab every 2 weeks.

What did the study find regarding tolerability and dose?

The maximum tolerated dose was 25 mg pixatimod in combination with 240 mg nivolumab, and the combination was reported as well tolerated, with grade 3–5 treatment-related adverse events occurring in a subset of participants.

Sep 24, 2026

Uploaded by nayy☆