Request Demo
Last update 14 Oct 2026
Setidegrasib
Last update 14 Oct 2026
Overview
Basic Info
Drug Type Proteolysis-targeting chimeras (PROTAC) |
Synonyms ASP 3082, ASP-3082, ASP3082 |
Target |
Action degraders |
Mechanism KRAS G12D degraders(GTPase KRas G12D degraders) |
Therapeutic Areas |
Inactive Indication- |
Originator Organization |
Inactive Organization- |
License Organization- |
Drug Highest PhasePhase 3 |
First Approval Date- |
Regulation- |
Login to view timeline
Structure/Sequence
Molecular FormulaC60H65FN12O7S |
InChIKeyXXWMEQMGQNHRAF-WFJRNIGCSA-N |
CAS Registry2821793-99-9 |
Related
6
Clinical Trials associated with SetidegrasibNCT07773129
A Phase 1, Open-label Study to Evaluate the Metabolism and Excretion of [14C]ASP3082 in Healthy Adult Male Participants
Setidegrasib (ASP3082) is being developed for certain cancers. In this study, the researchers want to understand how it is processed by the body in healthy male volunteers.
To do this, [14C] which is a certain chemical (called a tracer, or radionuclide) has been added to setidegrasib. [14C] gives off radiation, but the dose is very low (about the same as the dose from an x-ray) and will leave the body within a few days. [14C] will be picked up by a scanner and will be used to follow setidegrasib through the body. [14C]setidegrasib will be given as 1 single injection slowly through a vein (infusion).
The men will stay overnight in the clinic for at least 2 weeks. They will give regular blood, urine and stool samples during their stay and will be closely monitored. The men will return to the clinic about 1 week later for a final safety check.
To do this, [14C] which is a certain chemical (called a tracer, or radionuclide) has been added to setidegrasib. [14C] gives off radiation, but the dose is very low (about the same as the dose from an x-ray) and will leave the body within a few days. [14C] will be picked up by a scanner and will be used to follow setidegrasib through the body. [14C]setidegrasib will be given as 1 single injection slowly through a vein (infusion).
The men will stay overnight in the clinic for at least 2 weeks. They will give regular blood, urine and stool samples during their stay and will be closely monitored. The men will return to the clinic about 1 week later for a final safety check.
Start Date28 Aug 2026 |
Sponsor / Collaborator |
NCT07566052
A Randomized, Open-label, Phase 3 Study of Setidegrasib (ASP3082) Versus Docetaxel in Participants With KRAS G12D-mutated Locally Advanced (Unresectable) or Metastatic Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on or After Platinum Based Chemotherapy and Checkpoint Inhibitor Therapy (CPI)
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The first treatment is usually chemotherapy, given with another treatment that targets specific proteins on cancer cells. If the cancer gets worse, the next main treatment is usually a medicine called docetaxel. This treatment doesn't stop most people's cancer from getting worse for very long. Other treatments are needed to improve outcomes in people with NSCLC.
Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with NSCLC have a faulty KRAS gene in their tumor. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation.
Setidegrasib (ASP3082) is thought to remove some of the abnormal proteins made from the faulty KRAS gene. Before setidegrasib can become available as a treatment, studies need to be done.
This study is for people with NSCLC with a faulty KRAS gene in their tumor. In this study, some people will be given setidegrasib and some people will be given docetaxel. The main aims are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel, and if they live for longer. Other aims are to check tumor response, symptoms, how the body processes setidegrasib, and its safety, compared with docetaxel.
The main aims of study are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel and if people who are given setidegrasib live for longer compared to people who are given docetaxel.
People in this study will be adults with locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) with the G12D mutation in their KRAS gene. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They have had no more than 2 previous treatments for their cancer. The key reasons people cannot take part are if they have different faulty genes in their tumor which can be targeted with other treatments, have symptomatic or untreated cancers that have spread from the lung into the brain or nervous system, their cancer has spread to the thin tissue that covers the brain and spinal cord (leptomeningeal disease), or they have recently had other active cancers that required treatment.
In this study, people will either receive setidegrasib or docetaxel. Whether people receive setidegrasib or docetaxel is decided by chance, not by the study doctor. Both study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. Some people on docetaxel may be able to switch to setidegrasib during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study. People will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After people's cancer becomes worse, clinic staff will telephone people every 12 weeks to check on their cancer.
Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with NSCLC have a faulty KRAS gene in their tumor. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation.
Setidegrasib (ASP3082) is thought to remove some of the abnormal proteins made from the faulty KRAS gene. Before setidegrasib can become available as a treatment, studies need to be done.
This study is for people with NSCLC with a faulty KRAS gene in their tumor. In this study, some people will be given setidegrasib and some people will be given docetaxel. The main aims are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel, and if they live for longer. Other aims are to check tumor response, symptoms, how the body processes setidegrasib, and its safety, compared with docetaxel.
The main aims of study are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel and if people who are given setidegrasib live for longer compared to people who are given docetaxel.
People in this study will be adults with locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) with the G12D mutation in their KRAS gene. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They have had no more than 2 previous treatments for their cancer. The key reasons people cannot take part are if they have different faulty genes in their tumor which can be targeted with other treatments, have symptomatic or untreated cancers that have spread from the lung into the brain or nervous system, their cancer has spread to the thin tissue that covers the brain and spinal cord (leptomeningeal disease), or they have recently had other active cancers that required treatment.
In this study, people will either receive setidegrasib or docetaxel. Whether people receive setidegrasib or docetaxel is decided by chance, not by the study doctor. Both study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. Some people on docetaxel may be able to switch to setidegrasib during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study. People will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After people's cancer becomes worse, clinic staff will telephone people every 12 weeks to check on their cancer.
Start Date28 Apr 2026 |
Sponsor / Collaborator |
NCT07483983
Phase 2, Multicenter, Open Label, Platform Study Investigating ASP3082 in Patients With Metastaic/Locally Non-Small-Cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC), With Biomarker Analysis to Characterize Response/Resistance
UNLOCK ASP3082 is an open label, single arm, multicenter, phase 2 platform study that aims to evaluate the mechanisms of action and resistance to ASP3082 in metastatic/locally advanced Non-Samll-Cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC) with the presence of KRAS G12D mutation. The two cohorts of patients are the following : i. cohort NSCLC : patients with NSCLC with KRAS G12D mutation. ii. cohort PDAC : patients with PDAC with KRAS G12D mutation. Patients enrolled in the both cohorts will receive treatment with ASP3082 at the dose of 600 mg QW thereafter in a 21-day cycle. ASP3082 will be administred in intravenous route until disease progression, unacceptable toxicity, or consent withdrawal. Tumor and blood samples will be collected at baseline, on-treatment and at the end of treatment visit only from patients who develop acquired resistance (acquired resistance is defined as a best response of CR, PR, or SD lasting more than 6 months, followed by PD).
Start Date25 Mar 2026 |
Sponsor / Collaborator |
100 Clinical Results associated with Setidegrasib
Login to view more data
100 Translational Medicine associated with Setidegrasib
Login to view more data
100 Patents (Medical) associated with Setidegrasib
Login to view more data
6
Literatures (Medical) associated with Setidegrasib09 Apr 2026·NEW ENGLAND JOURNAL OF MEDICINE
Setidegrasib in Advanced Non–Small-Cell Lung Cancer and Pancreatic Cancer
Article
Author: Hollebecque, Antoine ; Inagaki, Chiaki ; Kitano, Shigehisa ; Cui, Daniel ; You, Benoît ; Lu, Ying ; Saito, Takeshi ; Cassier, Philippe A. ; Kadam, Shilpa ; Nishina, Tomohiro ; Jung, Minkyu ; Berlin, Jordan D. ; Herzberg, Benjamin O. ; Ueno, Makoto ; Paz-Ares Rodríguez, Luis ; Pelster, Meredith S. ; Morgensztern, Daniel ; Fountzilas, Christos ; Wang, Judy S. ; Tolcher, Anthony W. ; Kasi, Anup ; Park, Wungki ; LoRusso, Patricia ; Macarulla, T ; Gill, Stanley C. ; Shetty, Aditya ; Italiano, Antoine ; Kuboki, Yasutoshi ; Sakai, Daisuke ; Shoji, Hirokazu ; Toyoshima, Junko ; Jänne, Pasi A. ; Spira, Alexander I. ; Goldman, Jonathan W. ; Kim, Sang-We ; Fujii, Hisaki
BACKGROUND:
The KRAS p.G12D variant occurs in 5% of patients with non-small-cell lung cancer (NSCLC) and is the most common substitution variant in pancreatic ductal adenocarcinoma, occurring in 40% of patients, but no targeted therapies directed against this variant are currently approved for clinical use. Setidegrasib (ASP3082) is a first-in-class KRAS G12D-targeted protein degrader.
METHODS:
We conducted this phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of setidegrasib in patients with previously treated advanced solid tumors harboring KRAS p.G12D variants. The primary objectives were to evaluate the safety profile, as indicated by dose-limiting toxic effects and adverse events (the primary end points), and to determine the phase 2 dose. Setidegrasib was administered intravenously once weekly at doses of 10 to 800 mg.
RESULTS:
Overall, 203 patients were enrolled. Among the 76 patients who received setidegrasib at a dose of 600 mg, which was ultimately selected as the phase 2 dose, adverse events occurred during treatment in all the patients, with events of grade 3 or higher in 42%. Treatment-related adverse events occurred in 93% of the patients; the most common were transient infusion-related reactions (in 80%) and nausea (in 30%). Adverse events led to discontinuation in 2 patients. Among the 45 patients with NSCLC who received the 600-mg dose, 36% (95% confidence interval [CI], 22 to 51) had a partial response, the median progression-free survival was 8.3 months (95% CI, 4.1 to could not be estimated), and the estimated 12-month overall survival was 59% (95% CI, 40 to 74). Among the 21 patients with metastatic pancreatic ductal adenocarcinoma who received the 600-mg dose as second- or third-line treatment (of whom 67% received setidegrasib as third-line treatment), 24% (95% CI, 8 to 47) had a response, the median progression-free survival was 3.0 months (95% CI, 1.4 to 6.9), and the median overall survival was 10.3 months (95% CI, 4.2 to 13.0).
CONCLUSIONS:
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.).
12 Jan 2026·Cancer Discovery
“The RAS Dam Has Broken”
Article
ASP3082, a proteolysis targeting chimera that targets mutant KRASG12D, and elironrasib, a tri-complex inhibitor of KRASG12C in the “on” state, showed encouraging efficacy and safety in separate phase I trials.
MEDICAL ONCOLOGY
Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers
Review
Author: Arya, Swati ; Grover, Madhuri ; Parveen, Hiba ; Yadav, Divya ; Chatterjee, Srijita ; Sharma, Nidhi
One of the most commonly mutated oncogenes is Kirsten rat sarcoma viral oncogene homolog (KRAS, which is found in nearly all pancreatic ductal adenocarcinomas (PDAC), is commonly found in colorectal cancers (CRC), and is found in significant numbers in non-small-cell lung cancers (NSCLC). For most of its history, KRAS has been regarded as "undruggable." Still, with recent developments in covalent inhibitors targeting KRAS^G12C, specifically sotorasib and adagrasib, it has now been validated as a viable therapeutic target. Unfortunately, most KRAS mutations occur outside KRAS^G12C and thus require alternative therapeutic strategies beyond those already available. This review summarizes the fast-moving developments in the world of allele-specific and pan-KRAS inhibitors with reference to patent filings, clinical trials, and combinations with other agents. New classes of KRAS inhibitors have recently emerged, including non-covalent inhibitors (MRTX1133, RMC-9805), pan-RAS (ON) antagonists (RMC-6236), and KRAS-directed degraders (ASP3082), as well as planned rational combinations of these new KRAS inhibitors with agents targeting SHP2, SOS1, MEK, and immune checkpoint inhibitors. Other factors, including the development of innovative drug delivery systems, the exploration of resistance mechanisms, and the pursuit of synthetic lethality, could facilitate the complexity of treating KRAS-driven cancers. The regulatory environment and commercialization efforts present opportunities and challenges for precision oncology in KRAS-driven cancers globally. Overall, the rapid evolution of KRAS-targeted therapeutic agents represents a shift from allele-specific inhibition towards a strategy that is mutation/context-dependent, thereby creating further clinical translation opportunities and increased patient benefit.
19
News (Medical) associated with Setidegrasib12 Oct 2026
iStock,
Yutthana Gaetgeaw
Data released by the FDA show that Revolution Medicine’s newly approved pancreatic cancer drug underperformed in a large subgroup of patients, but analysts say the biotech still has a clear winner.
A little over a month after Revolution Medicines received an
early FDA approval
for its RAS inhibitor Rasonque in pancreatic adenocarcinoma,
review documents
released by the agency showed that a subtype of patients had a lower objective response rate than others. While the biotech’s stock dropped more than 6% last Thursday on the news, analysts largely saw the investor reaction as overblown.
Rasonque reached a 33% objective response rate (ORR) across all KRAS mutations in the Phase 3 RASolute 302 trial, but digging deeper into that figure showed that certain subgroups fared better, as others performed worse. While patients with a G12V mutation, representing 36% of study participants, achieved an ORR of 50%, the drug’s performance in those with G12D mutations, which represented 43% of the trial’s population, led to an ORR of just 24%.
A smaller cohort with G12R mutations was the weakest subgroup with a 7% ORR, lower even than the control group that received chemotherapy. Patients with G12R mutations represent a small portion of the pancreatic cancer population, RevMed said.
Still, analysts expect a record launch for Rasonque. Prior to the newest FDA document release, analysts at Leerink Partners said that “we think this may earn a place as one of the top oncology launches of all time.”
Cancer
RevMed could become ‘next oncology titan’ with Rasonque nod
A future expansion of Rasonque into first-line pancreatic ductal adenocarcinoma could set Revolution Medicines up to hit $2.3 billion in sales by 2028, according to Truist Securities.
August 27, 2026
·
2 min read
·
Tristan Manalac
Read more
Rasonque’s approval, which arrived months ahead of schedule, was based on
overall survival of 13.2 months
compared to 6.7 months for patients receiving chemotherapy. At the time, the FDA’s Oncology Center of Excellence director Angelo de Claro said the early approval was the result of “unprecedented results in an area of high unmet need,” in a disease with a five-year survival rate of just 13%. The data received widespread acclaim and greased the wheels for a quick regulatory push, which included a Commissioner’s National Priority Voucher.
Upon release of the subtype data, Leerink analysts were still bullish on RevMed’s ability to hold strong in the KRAS market, calling it “premature to assume” that Rasonque would lose its position in G12D mutation subtypes. They cited robust progression-free survival (PFS) and overall survival (OS) data, as well as RevMed’s ongoing development program with multiple approaches to KRAS mutations across subtypes.
Similarly, Truist Securities analysts called the release “a small crack in the data” that would be unlikely to change RevMed’s market trajectory in the long run.
“While the divergence warrants attention, we see more nuance, than a fundamental challenge to our RevMed PDAC thesis,” Truist analysts wrote to investors on Oct. 8. “We note that in these new data, G12D efficacy remains clinically meaningful across ORR, PFS and OS, and these exploratory analyses were not powered for cross-mutation comparisons.”
The analysts added that Rasonque is already positioned as the new second-line pancreatic adenocarcinoma standard of care with no nearby competitors in the RAS/KRAS space.
Still, even the small gap in RevMed’s data could provide an opening for others developing KRAS-based treatments in pancreatic cancer. In particular, Astellas’ setidegrasib, currently in Phase 3 studies, is designed to specifically target the G12D mutation. Analysts from Jefferies wrote in a Monday note that Rasonque’s weakness there could be a competitive opportunity for Astellas.
Phase 3Clinical ResultDrug Approval
07 Oct 2026
– PADCEV™ (enfortumab vedotin) plus pembrolizumab data highlight durable survival benefit in advanced bladder cancer –
– VYLOY™ (zolbetuximab) research reinforces the role of CLDN18.2 in shaping gastric cancer treatment decisions –
TOKYO, October 7, 2026 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced that 21 abstracts from its oncology portfolio will be presented at the European Society for Medical Oncology Congress 2026 (ESMO 2026), taking place October 23–27 in Madrid, Spain. The presentations span prostate, urothelial, gastric/gastroesophageal junction (GEJ), lung and pancreatic cancers, reflecting Astellas’ commitment to advancing standards of care and pursuing new scientific approaches designed for cancers where significant unmet need remains.
Moitreyee Chatterjee-Kishore, Ph.D., MBA, Executive Vice President and Head of Oncology Development, Astellas: “Standards of care do not change by accident. The data being presented at ESMO 2026 demonstrate how a deep understanding of disease biology and differentiated modalities is helping advance care for patients with bladder, gastric, and prostate cancers, including through approaches such as PADCEV™ (enfortumab vedotin) plus pembrolizumab, VYLOY™ (zolbetuximab), and XTANDI™ (enzalutamide). We are building upon this knowledge to develop the next generation of therapeutic options for cancers where unmet needs remain and look forward to engaging in discussions about this work at the congress.”
Highlights from Astellas’ ESMO 2026 presentations include:
Enfortumab vedotin plus pembrolizumab presentations include the longest follow-up reported to date in locally advanced or metastatic urothelial cancer, along with analyses across patient subgroups and treatment settings. Additional presentations include trials in progress exploring bladder preservation in muscle-invasive bladder cancer. Zolbetuximab presentations examine CLDN18.2 assessment, patient identification and real-world use, reinforcing the growing body of evidence supporting CLDN18.2-guided treatment decisions in gastric and GEJ cancers. Pipeline presentations feature trials-in-progress across Astellas’ investigational programs, including Phase 3 trials of setidegrasib in KRAS G12D-mutated pancreatic and non-small cell lung cancers, a Phase 1 trial of ASP5834 in KRAS-mutated or amplified solid tumors, and a Phase 1b/2 trial of ASP546C in CLDN18.2-expressing solid tumors. Together, these investigational studies illustrate Astellas’ continued investment in advancing new approaches aimed at overcoming challenges that have limited progress in hard-to-treat cancers.
Additional details on Astellas’ presentations at ESMO 2026 are included below.
About Astellas Astellas is a global life sciences company committed to turning innovative science into value for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.
About PADCEV and the Pfizer, Astellas and MSD Collaboration Seagen and Astellas previously entered a clinical collaboration agreement with MSD to evaluate the combination of Seagen’s and Astellas’ PADCEVTM (enfortumab vedotin) and MSD’s KEYTRUDA® (pembrolizumab) in patients with urothelial cancer. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).
About XTANDI and the Pfizer/Astellas Collaboration In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a commercial agreement to jointly develop and commercialize XTANDI® (enzalutamide) in the United States, while Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing the product outside the United States. Pfizer receives alliance revenues as a share of U.S. profits and receives royalties on sales outside the U.S.
Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions, and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’ intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
Contacts for inquiries or additional information: Astellas Pharma Inc. Corporate Communications +81-3-3244-3201
Phase 1AcquisitionPhase 3License out/in
23 Sep 2026
- Study evaluates novel, investigational KRAS G12D-targeted protein degrader setidegrasib versus docetaxel in previously treated patients with advanced NSCLC
-
- Milestone marks second Phase 3 study of setidegrasib initiated within six months -
TOKYO
,
Sept. 23, 2026
/
PRNewswire
/ --
Astellas
Pharma
Inc. (
TSE
: 4503, President and CEO:
Naoki
Okamura
, "
Astellas
") today announced that the first patient has been dosed in a Phase 3 study evaluating
setidegrasib
,
a novel, investigational
KRAS
G12D-targeted protein
degrader
, versus
docetaxel
in people with
KRAS
G12D-mutated locally advanced (
unresectable
) or metastatic non-small cell lung cancer (
NSCLC
) whose disease has progressed on or after initial platinum-based chemotherapy and checkpoint inhibitor therapy (CPI).
1
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, with
NSCLC
accounting for approximately 80% of cases.
2
,
3
Around 5% of people with
NSCLC
have a
KRAS
G12D mutation.
4
Despite advances in targeted treatment for other
molecularly
defined forms of
NSCLC
, there are currently no therapies approved specifically for people with
KRAS
G12D-mutated
NSCLC
.
3
,
5
Patients whose disease progresses on or after initial treatment currently rely on standard systemic options, such as chemotherapy.
5
Setidegrasib
is an investigational targeted protein
degrader
designed to degrade and eliminate the disease-driving
KRAS
G12D protein. By removing this protein,
setidegrasib
may help disrupt cancer cell signaling and destroy cancer cells.
4
This Phase 3 study in previously treated
NSCLC
builds on early clinical evidence published in
The New England Journal of Medicine
in March 2026, which demonstrated
antitumor
activity and a manageable safety pro patients with
KRAS
G12D-mutated solid tumors, supporting the proposed mechanism of action of
setidegrasib
.
4
Hidenori
Kitai
, M.D.,
Ph
.D., Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Japan:
"For too long, patients with
KRAS
G12D-mutated non-small cell lung cancer have had limited treatment options after standard therapies. This Phase 3 study represents an important step forward for the field, helping to build the evidence needed to understand whether
setidegrasib
could offer a potential new approach for this
molecularly
defined patient population."
Tadaaki
Taniguchi
, M.D.,
Ph
.D., Chief Research and Development Officer,
Astellas
:
"The initiation of this Phase 3 study in
NSCLC
, our second Phase 3 study of
setidegrasib
within six months, reflects continued progress in its clinical development. This study will help us understand how
setidegrasib's
novel approach to degrading disease-driving
KRAS
G12D may help address unmet needs for patients with this type of
NSCLC
. We are grateful to the patients, investigators and study teams making this research possible."
Setidegrasib
is
Astellas
' lead investigational targeted protein
degrader
. Initiation of the Phase 3 study in previously treated patients with
NSCLC
supports
Astellas
' Corporate Strategic Plan, with an ambition to initiate five or more Phase 3 or pivotal studies by fiscal year 2027. It follows the
initiation of a Phase 3 study of
setidegrasib
in front-line pancreatic
ductal
adenocarcinoma (
PDAC
)
in April 2026.
6
To further inform the scientific understanding of
setidegrasib
and
KRAS
G12D-driven disease biology,
Astellas
will also present
translational
analyses from the Phase 1 study of
setidegrasib
in patients with
KRAS
G12D-mutated
PDAC
at the upcoming
AACR
Conference on Pancreatic Cancer, September 25–28, 2026.
7
,
8
The analyses will provide further insight into mechanisms of response, resistance and potential rational combination approaches in pancreatic cancer. The findings will be featured in both a proffered oral presentation and a poster presentation.*
* Presentation details at
AACR
Conference on Pancreatic Cancer
Title:
Integrated
translational
analyses of the first-generation
KRAS
G12D
degrader
setidegrasib
identify mechanisms of response and resistance and offer rational combination strategies
Lead author:
Wungki
Park, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center
Details: Poster Presentation:
Poster Number: B040, Date: September 27, 2026, 5:00–7:00 p.m. PT;
Oral Presentation (short talk from proffered abstract):
Abstract Number: PR014 B040, Date: September 28, 2026, 9:42 a.m. PT.
About the Phase 3
NSCLC
Study
1
The randomized, open-label Phase 3 study is evaluating
setidegrasib
compared with
docetaxel
in people with
KRAS
G12D-mutated locally advanced (
unresectable
) or metastatic
NSCLC
whose disease has progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy (CPI). The dual primary endpoints are progression-free survival (
PFS
), assessed by blinded independent central review, and overall survival (OS).
Astellas
plans to enroll approximately 356 patients across multiple countries into the study.
About
setidegrasib
4
,
9
,
10
Setidegrasib
is a novel, investigational targeted protein
degrader
designed to degrade and eliminate the disease-driving
KRAS
G12D protein. By removing this protein,
setidegrasib
may help disrupt cancer cell signaling and destroy cancer cells. Discovered and advanced through
Astellas
' in-house R&D capabilities,
setidegrasib
is designed to work with the cancer cell's own protein degradation machinery to bring together the
KRAS
G12D protein and an E3
ligase
. This triggers selective degradation of the disease-driving protein, providing a distinct approach to targeting this cancer-driving mutation.
For more information on the Phase 3 study of
setidegrasib
in previously treated
NSCLC
, visit
ClinicalTrials
.gov and search for identifier
NCT
07566052
. For more information about the Phase 3 study of
setidegrasib
in front-line
PDAC
, visit
ClinicalTrials
.gov and search for identifier
NCT
07409272
.
The safety and efficacy of
setidegrasib
have not been established for the uses being considered. There is no guarantee that
setidegrasib
will receive regulatory approval and become commercially available for the uses being investigated.
About
Astellas
' Corporate Strategic Plan
Learn more at
www
.
astellas
.com/en/about/corporate-strategic-plan
.
About
Astellas
Astellas
is a global life sciences company committed to turning innovative science into value for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at
www
.
astellas
.com
.
Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of
Astellas
. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions, and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of
Astellas
to market existing and new products effectively, (v) the inability of
Astellas
to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of
Astellas
' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
References
ClinicalTrials
.gov. U.S. National Library of Medicine. A Study to Compare
Setidegrasib
(ASP3082) With
Docetaxel
, in People With Non-small Cell Lung Cancer With a
KRAS
G12D Mutation. Identifier:
NCT
07566052. Available at:
https
://
clinicaltrials
.gov/study/
NCT
07566052
. Last accessed September 21, 2026.
World Health Organization. 2026. Lung cancer. Available at:
https
://
www
.who.int/news-room/fact-sheets/detail/lung-cancer
. Last accessed September 21, 2026.
Tang Y,
et
al
. Targeting
KRASG
12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential.
Cancer Gene
Ther
. 2024;31(7):961-969.
doi
:10.1038/s41417-024-00778-4.
Park W,
et
al
.
Setidegrasib
in advanced non-small-cell lung cancer and pancreatic cancer.
N
Engl
J Med
. 2026;394(14):1409-1420.
doi
:10.1056/
NEJMoa
2600752.
Reuss
et
al
. Therapy for stage IV non-small cell lung cancer without driver alterations:
ASCO
Living Guideline.
J
Clin
Oncol
. 2026;44(7):e56-e88.
doi
:10.1200/
JCO
-25-02825.
ClinicalTrials
.gov. U.S. National Library of Medicine. A Study to Evaluate the Effectiveness and Safety of
Setidegrasib
, Given With Either
mFOLFIRINOX
or
NALIRIFOX
Chemotherapies
, in People With Pancreatic Cancer. Identifier:
NCT
07409272. Available at:
https
://
clinicaltrials
.gov/study/
NCT
07409272
. Last accessed September 21, 2026.
Park W. Integrated
translational
analyses of the first-generation
KRAS
G12D
degrader
setidegrasib
identify mechanisms of response and resistance and offer rational combination strategies. Oral presentation at:
AACR
Conference on Pancreatic Cancer; September 25–28, 2026; San Diego, CA.
Park W,
et
al
. Integrated
translational
analyses of the first-generation
KRAS
G12D
degrader
setidegrasib
identify mechanisms of response and resistance and offer rational combination strategies. Poster presented at:
AACR
Conference on Pancreatic Cancer; September 25–28, 2026; San Diego, CA.
Yoshinari
T,
et
al
. Discovery of
KRAS
(G12D) selective
degrader
ASP3082.
Commun
Chem
. 2025;8:254.
Paz
-Ares L,
et
al
. Efficacy and safety of
setidegrasib
in patients with advanced
NSCLC
with
KRAS
G12D mutation. Presented at: European Lung Cancer Congress (
ELCC
) 2026; March 25, 2026; Copenhagen, Denmark. Abstract 1O.
View original content to download multimedia:
SOURCE Astellas Pharma Inc.
Phase 3Phase 1AACRClinical Result
100 Deals associated with Setidegrasib
Login to view more data
R&D Status
10 top R&D records. to view more data
Login
| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| metastatic non-small cell lung cancer | Phase 3 | China | 03 Aug 2026 | |
| KRAS G12D mutation Non-small cell lung cancer | Phase 3 | United States | 28 Apr 2026 | |
| KRAS G12D mutation Non-small cell lung cancer | Phase 3 | Japan | 28 Apr 2026 | |
| Pancreatic Ductal Adenocarcinoma | Phase 3 | United States | 24 Feb 2026 | |
| Pancreatic Ductal Adenocarcinoma | Phase 3 | China | 24 Feb 2026 | |
| Pancreatic Ductal Adenocarcinoma | Phase 3 | Japan | 24 Feb 2026 | |
| Metastatic Pancreatic Cancer | Phase 3 | United States | 17 Feb 2026 | |
| Metastatic Pancreatic Cancer | Phase 3 | China | 17 Feb 2026 | |
| Metastatic Pancreatic Cancer | Phase 3 | Japan | 17 Feb 2026 | |
| Metastatic Pancreatic Cancer | Phase 3 | South Korea | 17 Feb 2026 |
Login to view more data
Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
| Study | Phase | Population | Analyzed Enrollment | Group | Results | Evaluation | Publication Date |
|---|
Phase 1 | 20 | qwpflnorpx(iikldomxqz) = zideaaptri qcwtimizkp (hrarlaxini ) View more | Positive | 02 Jul 2026 | |||
(BTC) | rhaswziwim(bkhamaxugh) = hilezrqjpd uxuddzjqcl (yomfehixqf ) View more | ||||||
Phase 1 | Pancreatic Ductal Adenocarcinoma KRAS G12D | 42 | cakyxgyohj(nkdlkdqllg) = ubkcmmlzib romkwrbcts (uxpoubxzbn ) | Positive | 08 Jan 2026 | ||
cakyxgyohj(nkdlkdqllg) = klejygdurg romkwrbcts (uxpoubxzbn ) View more | |||||||
NCT05382559 (ESMO2024) Manual  | Phase 1 | 98 | ASP3082 10 mg | uwwrjvydes(xltvbinacr) = ajkvldoskm arzpbublmd (fubajxhyyg ) View more | Positive | 15 Sep 2024 | |
skoafaqsjd(cwsvjnqxgt) = ptppzxwfdd fonbkiivve (pslebeawiy ) View more |
Login to view more data
Translational Medicine
Boost your research with our translational medicine data.
login
or
Deal
Boost your decision using our deal data.
login
or
Core Patent
Boost your research with our Core Patent data.
login
or
Clinical Trial
Identify the latest clinical trials across global registries.
login
or
Approval
Accelerate your research with the latest regulatory approval information.
login
or
Regulation
Understand key drug designations in just a few clicks with Synapse.
login
or
Hiro LS Researcher
The AI Search Engine Built to Accelerate Biopharma Decisions
Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.
Ask any biopharma research question→
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Discover Synapse Data Servers
Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!
Bio
Bio Sequences Search & Analysis
Sign up for free
Chemical
Chemical Structures Search & Analysis
Sign up for free