1723MO - Axitinib plus avelumab in patients with unresectable/metastatic gastrointestinal stromal tumor (GIST) after failure of standard therapy: Single-arm phase II study (AXAGIST)

Background

The development of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of advanced GIST, but new strategies are needed to overcome resistance mechanisms that promote disease progression. As VEGF inhibitors are considered to have immunomodulatory effects, we hypothesized that the combination of VEGF and PD-L1 inhibitors may have a synergistic effect and enhance the efficacy of both therapies.

Methods

AXAGIST (NCT04258956) was a two-centre, single-arm, phase II, two-stage trial designed to evaluate the efficacy and safety of avelumab (10 mg/kg iv Q2W) in combination with axitinib (5 mg po BID) in patients (pts) with unresectable/metastatic GIST after failure of standard therapy. The primary endpoint was progression-free survival at 3 months based on RECIST 1.1 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety.

Results

Of the 58 pts enrolled, 56 pts were evaluable for safety and efficacy. Median age was 60 years (range 18-80), 21 pts (37.5%) were female and 30 pts (53.6%) had received prior 3 lines of TKIs. Median follow-up was 27.4 months (95% CI, 25.4-NA). The best response was partial response in 5 pts (8.9%), stable disease in 34 pts (60.7%) and progressive disease in 17 pts (30.4%). Among pts with partial response, the median duration of response was 18.5 months (95%CI, 18.3-NA). The PFS rate at 3 months was 57.1%. Median PFS and OS were 4.6 months (95%CI, 2.9-6.4) and 14.2 months (95%CI, 9.2-26.3), respectively. The 12-month PFS and OS rates were 22.8% (95% CI: 14-37.1) and 59.3% (95% CI: 47.5-74), respectively. Adverse events occurred in 94.6% of patients; 30.4% of patients experienced grade 3 or higher adverse events, all were manageable.

Conclusions

The results of this largest trial of combination of targeted therapy and immunotherapy in pretreated GIST shows significant efficacy of this novel therapeutic approach. A substantial subset of pts achieved long-term clinical benefit. Further correlations of biomarkers will be presented.

Clinical trial identification

NCT04258956.

Editorial acknowledgement

Legal entity responsible for the study

Maria Sklodowska-Curie National Research Institute of Oncology.

Funding

This research and drug supply s financially supported by Pfizer, and is part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer Inc. The study protocol was initially developed during 19th MCCR Workshop.

Disclosure

P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. T. Switaj: Financial Interests, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre. P. Rogala: Financial Interests, Invited Speaker: BMS, Novartis, MSD, Pierre Fabre. K. Kozak: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Sanofi. All other authors have declared no conflicts of interest.