Elraglusib improves survival in untreated metastatic pancreatic cancer

A randomised phase 2 study showed that elraglusib, a GSK-3β inhibitor, combined with gemcitabine/nab-paclitaxel, significantly improves overall survival (OS) in participants with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

In the phase 2 part of the 1801 trial (NCT03678883), participants with mPDAC (n=287) were randomised 2:1 to receive weekly elraglusib plus chemotherapy (n=155) or chemotherapy alone (n=78). Dr Devalingam Mahalingam (Northwestern Medicine, IL, USA) presented the preliminary results [1].

The median OS was 10.1 months in the elraglusib arm compared to 7.2 months with chemotherapy alone (HR 0.63; P=0.01), representing a 37% reduced risk of death. The 12-month OS also favoured the elraglusib arm with 44.1% over 22.3%. Similarly, the 18-month OS rates were 19.7% and 4.4%, and the  24-month OS rates were 13.8% versus 0% [2]. The median PFS rate touched 5.6 versus 5.1 months (HR 0.90), and time-to-treatment failure was 5.1 vs 3.4 months (HR 0.79) for elraglusib versus control, neither reaching statistical significance. The overall response rates were 29.0% compared to 21.8%, with a disease control rate of 61.3% and 56.4% for elraglusib and control, respectively. The median duration of response was 5.5 versus 4.0 months. Subgroup analyses favoured elraglusib for baseline liver metastases, ECOG performance status, and tumour marker CA-19.

Serious treatment-emergent adverse events occurred in 55.5% of the elraglusib group and 56.4% of the control group, leading to a discontinuation of treatment in 27.1% and 25.6%, respectively. Deaths due to treatment-emergent adverse events were 12.3% compared to 16.7% and treatment-related deaths were 0.05% and 0.02% for elraglusib and control arms, respectively. Visual impairment occurred in 67.7% of elraglusib-treated participants (vs 9.0%). Of these, only 0.6% were grade ≥3, and the rest were mild, transient, and reversible. Fatigue (any-grade/grade ≥3) was 62.6%/16.8% with elraglusib compared to 50.0%/5.1% with chemotherapy alone. Neutropenia (any-grade/grade ≥3) was more frequent with elraglusib at 61.3%/52.2% over 41.0%/30.8% in the control arm, but rates of febrile neutropenia and sepsis were similar.

Exploratory biomarker analyses suggested that high CXCL2 levels may predict a survival benefit with elraglusib (P=0.001 vs P=0.42 in control arm). Elraglusib also increased CD8⁺ and granzyme B⁺ cell infiltration, supporting its immunomodulatory activity.

“Elraglusib offers a potential new therapeutic avenue in mPDAC,” summarised Dr Mahalingam, adding that the early OS divergence suggests a durable survival benefit despite the aggressive nature of the disease.

1. Mahalingam D, et al. Preliminary results from the randomized phase 2 study (1801 part 3B) of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) versus GnP alone in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Combination Elraglusib + Chemotherapy Shows Overall Survival Benefit in Metastatic Pancreatic Cancer. Abstract #4006, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.
2. Mahalingam D, et al. ESMO Open. 2025;10(6):105122.

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Posted on 30 July 2025