ASP3082 / Astellas - LARVOL DELTA

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 | "Funded by Astellas Pharma Inc. Clinical Trial Registration Number: NCT05382559 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Biomarker • Clinical • P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Efficacy and safety of ASP3082 monotherapy or in combination with mFOLFIRINOX in patients (pts) with pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2026) - P1 | "Funded by Astellas Pharma Inc. Clinical Trial Registration Number: NCT05382559 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • Monotherapy • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • 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

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

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

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

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

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=356 | Recruiting | Sponsor: Astellas Pharma Inc | N=260 ➔ 356

Enrollment change • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Trial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations. (ASCO-GI 2023) - P1 | "Enrollment in Cohort 1 is complete, and enrollment to Cohort 2 began in September 2022. Clinical trial information: NCT05382559."

Clinical • Metastases • P1 data • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Novel KRAS G12D degrader ASP3082 demonstrates in vivo, dose-dependent KRAS degradation, KRAS pathway inhibition, and antitumor efficacy in multiple KRAS G12D-mutated cancer models (AACR 2023) - P1 | "ASP3082 is a potential therapeutic agent for patients with tumors harboring the KRAS G12D mutation. Currently, a phase 1 clinical trial is underway in patients with previously treated, locally advanced or metastatic solid tumors with KRAS G12D mutation (NCT05382559)."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • KRAS

ASP3082, a First-in-class novel KRAS G12D degrader, exhibits remarkable anti-tumor activity in KRAS G12D mutated cancer models (AACR-NCI-EORTC 2022) - P1 | "ASP3082 is a potential therapeutic agent for patients with tumors harboring the KRAS G12D mutation. Currently, Phase I clinical trial is underway (NCT05382559)."

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

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Astellas Pharma Inc | N=136 ➔ 240

Enrollment change • Colorectal Cancer • Oncology • Solid Tumor • KRAS

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=136 | Recruiting | Sponsor: Astellas Pharma Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • KRAS

A Study of ASP3082 in Adults With Previously Treated Solid Tumors (clinicaltrials.gov) - P1 | N=136 | Not yet recruiting | Sponsor: Astellas Pharma Inc

New P1 trial • Oncology • Solid Tumor • KRAS