setidegrasib (ASP3082) / Astellas - LARVOL DELTA

Efficacy and safety of setidegrasib in patients (pts) with advanced NSCLC with KRAS G12D mutation (ELCC 2026) - P1 | "Legal entity responsible for the study Astellas Pharma Inc. Funding Astellas Pharma Inc."

Clinical • First-in-human • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • KRAS • PD-L1

Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer. (PubMed, N Engl J Med) - P1 | "Setidegrasib was associated with antitumor activity and a low incidence of treatment discontinuation due to adverse events in patients with previously treated advanced KRAS p.G12D-mutated NSCLC or pancreatic ductal adenocarcinoma. (Funded by Astellas Pharma; ClinicalTrials.gov number, NCT05382559.)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Efficacy and safety of ASP3082 monotherapy or in combination with mFOLFIRINOX in patients (pts) with pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2026) - P1 | "We present results from this first-in-human study in pts with PDAC, including dose escalation and expansion, treated with ASP3082 or ASP3082 with modified folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX). ASP3082 showed promising antitumor activity alone or plus mFOLFIRINOX with no new safety signals in pts with PDAC. Findings support further evaluation of ASP3082 including DOR, progression-free survival, and overall survival in pts with KRAS G12D-mutant PDAC in both 1L and later-line settings."

Clinical • Combination therapy • First-in-human • Monotherapy • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Phase 1 evaluation of ASP3082, a first-in-class selective protein degrader, in patients (pts) with KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC): Pharmacokinetics (PK) and biomarker insights. (ASCO-GI 2026) - P1 | "ASP3082 induced robust KRAS G12D mutant protein degradation and inhibition of RAS-MAPK signaling in tumors. Findings indicate ctDNA KRAS G12D VAF is a prognostic and pharmacodynamic biomarker, supporting continued clinical development of ASP3082."

Biomarker • Clinical • P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • CEACAM5 • KRAS

UNLOCK ASP3082: Study Investigating ASP3082 in Patients With Metastatic/Locally Advanced Non-small-cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC), With Biomarker Analysis to Characterize Response/Resistance (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Biomarker • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • NTRK • ROS1

PBI-381, a development candidate PROTAC for KRasG12D solid tumors (AACR 2026) - "At present, ASP3082 (Astellas Pharma) and PT0253 (PAQ Therapeutics) are the only two KRasG12D PROTAC degraders that have entered clinical trials.Polymed Biopharmaceuticals has generated a series of potent and selective PROTAC molecules targeting the KRasG12D mutant protein. In head-to-head comparison studies using xenograft models, PBI-381 also exhibited significantly higher anti-tumor activity than ASP3082. IND-enabling activities on PBI-381 are underway to progress the compound further towards the clinic."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

3082-CL-0101: A Study of ASP3082 in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=681 | Recruiting | Sponsor: Astellas Pharma Inc | Trial completion date: Oct 2026 ➔ Dec 2027 | Trial primary completion date: Oct 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer (clinicaltrials.gov) - P3 | N=614 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

A Study to Learn How Fluconazole, Carbamazepine and Itraconazole Affect How the Body Processes ASP3082 in Healthy Adults (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • KRAS

CSET 2025/4116: Phase 2, Multicenter, Open label, Platform Study investigating ASP3082 in patients with Metastatic/Locally Advanced Non-Small-Cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC), with biomarker analysis to characterize response/resistance (UNLOCK ASP3082) (clinicaltrialsregister.eu) - P1/2 | N=60 | Not yet recruiting | Sponsor: Institut Gustave Roussy

Biomarker • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • NTRK • ROS1

A Study to Confirm the Safety of ASP3082, and if it Delays Tumor Growth in People With Pancreatic Cancer, When Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies (clinicaltrials.gov) - P3 | N=614 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

New P3 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

A Study to Learn How Fluconazole, Carbamazepine and Itraconazole Affect How the Body Processes ASP3082 in Healthy Adults (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

New P1 trial • KRAS

Efficacy and safety of ASP3082, a novel protein degrader, as monotherapy in patients (pts) with non-small cell lung cancer (NSCLC) with KRAS G12D mutation (AACR-NCI-EORTC 2025) - P1 | "Conclusions Consistent with findings from the dose escalation study, ASP3082 monotherapy showed promising antitumor activity in a heavily pretreated patient population with NSCLC; safety events were generally manageable. These findings support further evaluation of ASP3082 as a new first-in-class treatment option for pts with KRAS G12D-mutant solid tumors."

Clinical • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic (PC), colorectal (CRC), and non-small cell lung cancer (NSCLC) (ESMO 2024) - P1 | "The ongoing study suggests that ASP3082, a novel KRAS G12D degrader, has an acceptable safety profile and promising antitumor activity, especially in pts with heavily pretreated PC. Based on these results, further studies are needed."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Astellas to Present New Clinical Data Across Its Gastrointestinal Cancers Portfolio at 2026 ASCO GI Cancers Symposium (PRNewswire) - "Highlights include a late-breaking oral presentation of cohort results from the Phase 2 ILUSTRO study of first-line zolbetuximab in combination with chemotherapy and immunotherapy in claudin 18.2-positive, HER2-negative, locally advanced or metastatic G/GEJ cancer, as well as new Phase 1 data from ASP3082 (setidegrasib), an investigational KRAS G12D targeted protein degrader, in pancreatic cancer."

Clinical data • Late-breaking abstract • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Pancreatic Ductal Adenocarcinoma

Efficacy and safety of ASP3082, a novel protein degrader, as monotherapy in patients (pts) with non-small cell lung cancer (NSCLC) with KRAS G12D mutation (AACR-NCI-EORTC 2025) - P1 | "Conclusions Consistent with findings from the dose escalation study, ASP3082 monotherapy showed promising antitumor activity in a heavily pretreated patient population with NSCLC; safety events were generally manageable. These findings support further evaluation of ASP3082 as a new first-in-class treatment option for pts with KRAS G12D-mutant solid tumors."

Clinical • Late-breaking abstract • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Non-clinical study of ASP4396, a novel KRAS G12D degrader, shows remarkable anti-tumor activity in KRAS G12D mutant cancer models (AACR-NCI-EORTC 2025) - P1 | "A series of our non-clinical studies suggested that ASP4396 could be a promising therapeutic agent for patients with tumors harboring the KRAS G12D mutation. With these results, a Phase I clinical trial is underway (NCT06364696). We are conducting further characterization to understand the differences in the profiles of ASP3082 and ASP4396 due to the differences in E3 ligase and their impact on their respective efficacy and safety profiles."

Clinical • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Optimal efficacious dose prediction of a novel protein degrader ASP3082 selectively targeting KRAS G12D using quantitative systems pharmacology (AACR-NCI-EORTC 2025) - P1 | "The designed degradation QSP model was used to estimate the optimal efficacious dose in the ongoing first in human study (NCT05382559)."

Colorectal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Discovery of KRAS(G12D) selective degrader ASP3082. (PubMed, Commun Chem) - "ASP3082 effectively induces KRAS(G12D) protein degradation with remarkable selectivity, demonstrates highly efficacious and durable pharmacological activity, and induces tumor regression in multiple KRAS(G12D)-mutated cancer xenograft models. Our results suggest that ASP3082 is a potential therapeutic agent for KRAS(G12D)-mutated cancer, and is now under clinical investigation."

Journal • Oncology • Solid Tumor • Targeted Protein Degradation • Von Hippel-Lindau Syndrome • KRAS

Specific BaF3 tumor platform for c-KIT and KRAS mutations (AACR 2025) - "In this study, two specific BaF3 c-kit mutation tumor models (BaF3 c-KIT-V559-V560 del, BaF3 c-KIT-W557-K558 del-T670I) and BaF3 KRAS-G12C tumor models were established for efficacy evaluation of Imatinib, Sunitinib, and Sotorasib. Although ASP3082 is a KRAS G12D inhibitor, the efficacy of ASP3082-3 mpk to KRAS-G12D GP2d CDX model is not relevant, only 37.29% TGI and 73.25% T/C values were found in this study. Western blotting showed that the BaF3 mutation tumor models are suitable for the drug discovery of specific point mutation anti-cancer drugs."

Oncology • EGFR • KIT • KRAS

Combination effect of the KRAS G12D-specific degrader ASP3082 with Cetuximab in xenograft models of colorectal and pancreatic cancer cells with KRAS G12D mutation (EORTC-NCI-AACR 2024) - "Material and We investigated the combination effect of ASP3082 and EGFR inhibitors (Cetuximab, Afatinib and Lapatinib) on the growth of human cancer cells harboring KRAS G12D mutation by cell viability assay, and antitumor activity of the combination of ASP3082 and Cetuximab in mice subcutaneously xenografted with KRAS G12D-mutated colorectal and pancreatic cancer cells. ASP3082 and Cetuximab demonstrated a combination effect in KRAS G12D-positive colorectal and pancreatic cancer xenograft models. The pathway analysis is underway to elucidate the detailed mechanisms underlying the identified combination effects. This will enhance the therapeutic potential of our KRAS G12D degrader ASP3082 and the KRAS-targeted therapies, ultimately maximizing the patient value."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Astellas Presents Scientific Progress in Advanced and Hard-to-Treat Cancers at ESMO 2024 (Astellas Press Release) - "Astellas Pharma Inc...will highlight new data from across its approved and investigational cancer therapies during the 2024 European Society for Medical Oncology (ESMO) Congress being held in Barcelona, Spain on 13-17 September. Eight abstracts across a broad range of cancer types will be presented, reinforcing Astellas' commitment to making a meaningful difference to people living with advanced and hard-to-treat cancers. Six abstracts include data spanning prostate, urothelial, gastric and gastroesophageal junction (GEJ), and pancreatic cancers. Two abstracts feature Phase 1 data presented for the first time from immuno-oncology and targeted protein degradation assets."

Clinical data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Pancreatic Cancer • Prostate Cancer • Urothelial Cancer

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=541 | Recruiting | Sponsor: Astellas Pharma Inc | N=356 ➔ 541

Enrollment change • Metastases • Oncology • Solid Tumor • KRAS

Novel non-KRAS G12C inhibitors in solid tumors (YouTube) - "Alexander Spira, MD...provides an overview of non-KRAS G12C inhibitors for lung cancer and solid tumors, such as RMC-6236, which was assessed in the RMC-6236-001 trial (NCT05379985). In addition to lung cancer, the investigational pan-KRAS inhibitor was promising in pancreatic cancer, which has limited treatment options. KRAS G12D inhibitors under investigation include ASP3082 and RMC-9805. This interview took place at 2024 Targeted Therapies of Lung Cancer Meeting (TTLC 2024) in Santa Monica, CA."

Interview • Video

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=356 | Recruiting | Sponsor: Astellas Pharma Inc | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2026 ➔ Oct 2026

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS