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Setidegrasib (ASP3082)

First-in-human KRAS G12D targeted protein degrader

First-in-human phase 1 trial of setidegrasib, a first-in-class KRAS G12D targeted protein degrader, in advanced PDAC and NSCLC.

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Background

KRAS G12D is the most common KRAS variant in pancreatic cancer but has historically been undruggable. Setidegrasib (ASP3082) is a first-in-class targeted protein degrader designed to eliminate KRAS G12D protein rather than merely inhibit it.

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N Engl J Med · 2026

Setidegrasib in Advanced Non–Small-Cell Lung Cancer and Pancreatic Cancer

First-in-human phase 1 study of setidegrasib (ASP3082), a first-in-class KRAS G12D targeted protein degrader. Among 21 patients with previously treated metastatic PDAC receiving the 600 mg dose, 24% achieved objective response; median PFS and OS were 3.0 and 10.3 months. In NSCLC (n=45), ORR was 36% with median PFS of 8.3 months.

  • ORR 24% (PDAC)
  • mPFS 3.0 mo (PDAC)
  • Phase 1

Background

KRAS G12D is the most common KRAS variant in pancreatic cancer but has historically been undruggable. Setidegrasib (ASP3082) is a first-in-class targeted protein degrader designed to eliminate KRAS G12D protein rather than merely inhibit it.

Results

In this first-in-human phase 1 study, among 21 patients with previously treated metastatic PDAC receiving the 600 mg dose, 24% achieved an objective response; median PFS was 3.0 months and median OS was 10.3 months. Two-thirds of these patients received treatment in the third-line setting or later.

In NSCLC (n=45), the objective response rate was 36% with a median PFS of 8.3 months.