Efficacy and Safety of the Anti-IL1RAP Antibody Nadunolimab (CAN04) in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Advanced/Metastatic Pancreatic Cancer Article Swipe
Eric Van Cutsem
,
Joëlle Collignon
,
Rikke Løvendahl Eefsen
,
Sebastian Ochsenreither
,
Zanete Zvirbule
,
Audrius Ivanauskas
,
Dirk Arnold
,
Edita Baltruškevičienė
,
Per Pfeiffer
,
Jeffrey Yachnin
,
Susanne Magnusson
,
Camilla Rydberg Millrud
,
Annika Sanfridson
,
Nedjad Losic
,
Ignacio García-Ribas
,
Dominique Tersago
,
Ahmad Awada
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-24-0645
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-24-0645
Purpose: IL1 pathway upregulation is implicated in pancreatic ductal adenocarcinoma (PDAC) progression, therapy resistance, and survival. Nadunolimab is an IL1 receptor accessory protein (IL1RAP)–targeting antibody with enhanced antibody-dependent cellular cytotoxicity that blocks IL1α/IL1β signaling. We investigated efficacy and safety of nadunolimab in PDAC, in combination with gemcitabine/nab-paclitaxel (GN). Patients and Methods: Patients with previously untreated locally advanced/metastatic PDAC received nadunolimab (1.0–7.5 mg/kg) every 2 weeks with standard GN. The primary objective was safety; secondary objectives were antitumor response, progression-free survival, and overall survival (OS). Correlations between serum and tumor biomarkers and clinical response were explored. Results: Seventy-six patients were enrolled; the median age was 63 years (range, 43–89), 42% were female, 97% had metastatic disease, and 9% had received adjuvant chemotherapy. The most frequent grade ≥3 adverse event was neutropenia (66%), typically during cycle 1. Infusion-related reactions occurred in 29% (grade 3, 3%). Only 1 of the 76 patients had grade 3 or above peripheral neuropathy. No marked dose-dependent differences in safety or efficacy were observed among the four dose groups. The median OS was 13.2 months (95% confidence interval, 11.0–15.6), and the 1-year survival rate was 58%. The median immune PFS (immune Response Evaluation Criteria in Solid Tumours) was 7.1 months (95% confidence interval, 5.2–7.4). Treatment efficacy was higher in patients with high versus low tumor baseline IL1RAP expression (OS 14.2 vs. 10.6 months; P = 0.012). A reduction in serum IL8 on treatment correlated with prolonged OS. Conclusions: Nadunolimab combined with GN shows promising efficacy and manageable safety in locally advanced/metastatic PDAC. Higher tumor baseline IL1RAP expression correlated with better outcome.
Related Topics
Concepts
Gemcitabine
Medicine
Paclitaxel
Pancreatic cancer
Nab-paclitaxel
Oncology
Internal medicine
Deoxycytidine
Cancer
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.ccr-24-0645
- OA Status
- hybrid
- Cited By
- 4
- References
- 33
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4403308793
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4403308793Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/1078-0432.ccr-24-0645Digital Object Identifier
- Title
-
Efficacy and Safety of the Anti-IL1RAP Antibody Nadunolimab (CAN04) in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Advanced/Metastatic Pancreatic CancerWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-10-10Full publication date if available
- Authors
-
Eric Van Cutsem, Joëlle Collignon, Rikke Løvendahl Eefsen, Sebastian Ochsenreither, Zanete Zvirbule, Audrius Ivanauskas, Dirk Arnold, Edita Baltruškevičienė, Per Pfeiffer, Jeffrey Yachnin, Susanne Magnusson, Camilla Rydberg Millrud, Annika Sanfridson, Nedjad Losic, Ignacio García-Ribas, Dominique Tersago, Ahmad AwadaList of authors in order
- Landing page
-
https://doi.org/10.1158/1078-0432.ccr-24-0645Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1158/1078-0432.ccr-24-0645Direct OA link when available
- Concepts
-
Gemcitabine, Medicine, Paclitaxel, Pancreatic cancer, Nab-paclitaxel, Oncology, Internal medicine, Deoxycytidine, CancerTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
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2025: 4Per-year citation counts (last 5 years)
- References (count)
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33Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.2 | 64 |
| abstract_inverted_index.3 | 152 |
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