A Study of ASP3082 in Adults With Advanced Solid Tumors
A Phase 1 Study of ASP3082 in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation
4 other identifiers
interventional
681
7 countries
53
Brief Summary
This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP3082. The study aims to check how safe and well-tolerated ASP3082 is for people with advanced solid tumors that have a specific mutation called KRAS G12D. This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP3082 by itself, or together with cetuximab. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP3082, by itself or together with cetuximab, to use in Part 2 of the study. The first group will receive the lowest dose of ASP3082. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP3082. The panel will do this for each group until all groups have received ASP3082 (by itself or together with cetuximab) or until suitable doses have been selected for Part 2. In Part 2, ASP3082 will be given in by itself, or in combination with the other study treatments. Study treatments will be given through a vein. This is called an infusion. Each treatment cycle is 21 or 28 days long. They will continue treatment until: they have medical problems from the treatment they can't tolerate; their cancer gets worse; they start other cancer treatment; or they ask to stop treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2022
Longer than P75 for phase_1
53 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2022
CompletedFirst Posted
Study publicly available on registry
May 19, 2022
CompletedStudy Start
First participant enrolled
June 8, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
April 14, 2026
April 1, 2026
6.6 years
May 16, 2022
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Incidence of Dose Limiting Toxicities (DLTs)
A DLT is defined as any event meeting the DLT criteria excluding toxicities clearly related to disease progression or intercurrent illness or standard of care (SoC) regimens as determined by the investigator.
Up to 28 Days
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures.
Up to 48 months
Number of Participants with Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important events.
Up to 48 months
Number of Participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Up to 48 months
Number of Participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant ECG values.
Up to 48 months
Number of Participants with vital sign abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values.
Up to 48 months
Number of Participants with physical exam abnormalities and/or adverse events
Number of participants with potentially clinically significant physical exam values.
Up to 48 months
Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status
The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Up to 48 months
Secondary Outcomes (8)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Up to 48 months
Duration of Response (DOR) per RECIST v 1.1
Up to 48 months
Disease Control Rate (DCR) per RECIST v 1.1
Up to 48 months
Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)
Up to 48 months
PK of ASP3082 in plasma: Maximum Concentration (Cmax)
Up to 48 months
- +3 more secondary outcomes
Study Arms (11)
ASP3082 Dose Escalation (Monotherapy Part 1)
EXPERIMENTALParticipants will receive ASP3082 in a 21-day cycle.
ASP3082 Dose Expansion (Monotherapy Part 2)
EXPERIMENTALParticipants will receive ASP3082 with dose level(s) selected from dose escalation (part 1) in a 21-day cycle.
ASP3082 + Cetuximab Dose Escalation (Combination Therapy Part 1)
EXPERIMENTALParticipants will receive ASP3082 in a 21-day cycle. Cetuximab will be administered weekly.
ASP3082 + Cetuximab Dose Expansion (Combination Therapy Part 2)
EXPERIMENTALParticipants will receive ASP3082 or ASP3082 + Cetuximab with dose level(s) selected from dose escalation (part 1) in a 21-day cycle. Cetuximab will be administered weekly.
ASP3082 China Safety Cohort
EXPERIMENTALParticipants will receive ASP3082 with dose level selected from dose escalation (Monotherapy part 1) in a 21-day cycle.
Treatment naive PDAC cohort ASP3082 + FOLFIRINOX
EXPERIMENTALUpon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with FOLFIRINOX (leucovorin \[LV\]/fluorouracil \[5-FU\]/irinotecan/oxaliplatin) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.
Treatment naive PDAC cohort ASP3082 + Nab-Paclitaxel + Gemcitabine
EXPERIMENTALUpon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with Nab-P + GEM (nanoparticle albumin-bound-paclitaxel plus gemcitabine) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.
ASP3082 + Docetaxel - NSCLC
EXPERIMENTALParticipants with KRAS G12D mutant will receive ASP3082 in combination with docetaxel in a 21-day cycle.
ASP3082 + Pembrolizumab - NSCLC
EXPERIMENTALParticipants with KRAS G12D mutant will receive ASP3082 in combination with pembrolizumab in a 21-day cycle.
ASP3082 + (Cisplatin or Carboplatin) and Pemetrexed +/- Pembrolizumab - NSCLC
EXPERIMENTALParticipants with KRAS G12D mutant will receive ASP3082 in combination with platinum-based chemotherapy (cisplatin or carboplatin) and pemetrexed, with or without pembrolizumab in a 21-day cycle.
Treatment naive PDAC cohort ASP3082 + NALIRIFOX
EXPERIMENTALUpon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with NALIRIFOX (leucovorin\[LV\]/fluorouracil\[5-FU\]/liposomal irinotecan/oxaliplatin) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.
Interventions
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Eligibility Criteria
You may qualify if:
- Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog \[KRAS\] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive standard approved therapies (no limit to the number of prior treatment regimens).
- For the ASP3082 monotherapy escalation cohorts, participants with solid tumor malignancies are allowed to be enrolled. Participants with other known KRAS G12 mutations will not be eligible for the study
- For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX or NALRIFOX: Participant must have mPDAC that has not been previously treated with chemotherapy. If a participant received (neo)adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the (neo)adjuvant therapy.
- Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a tumor biopsy (core needle biopsy or excision) obtained after the last interventional treatment, but prior to start of study intervention. Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the study protocol. If a participant cannot provide a fresh tissue biopsy sample, the site should consult with the sponsor/study medical monitor.
- Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Participant has an ECOG performance status of 0, 1 or 2 for dose escalation, and 0 or 1 for dose expansion.
- Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of study intervention administration.
- Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of study intervention administration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids (NOTE: Physiologic replacement dose of hydrocortisone or its equivalent \[defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone\] is permitted), and not have active radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<= 2 weeks of radiotherapy) to non-central nervous system disease.
- Participant's adverse events \[AEs\] (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of study intervention (or prior to staring SoC chemotherapy, for first line (1L) participants receiving Nab-P+GEM FOLFIRINOX or NALIRIFOX.
- Participant has adequate organ function as indicated by protocol laboratory value parameters (If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 14 days after any blood transfusion.).
- Female participant is not pregnant, confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply:
- Not a woman of childbearing potential (WOCBP).
- WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after study intervention administration.
- EU only: For combination therapy with carboplatin, follow contraception guidelines from the time of informed consent through at least 7 months after the final dose of carboplatin.
- South Korea only: For combination therapy with oxaliplatin, follow contraception guidelines from the time of informed consent through at least 15 months after the final dose of oxaliplatin. For combination therapy with cisplatin, follow contraception guidelines from the time of informed consent through at least 14 months after the final dose of cisplatin.
- +7 more criteria
You may not qualify if:
- Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of study intervention.
- Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible.
- Participant has leptomeningeal disease as a manifestation of the current malignancy.
- Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
- Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used.
- Participant with active hepatitis B (including acute hepatitis B virus \[HBV\] or chronic HBV) or hepatitis C virus \[HCV\] (ribonucleic acid \[RNA\] detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing.
- Participant has a known history of human immunodeficiency virus \[HIV\] infection. No HIV testing is required unless mandated by a local health authority.
- Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention, left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QT syndrome.
- Participant has a corrected QT interval (single electrocardiogram \[ECG\]) using Fridericia's formula (QTcF) \> 450 milliseconds (msec) (men) or \>470 msec (women) during screening.
- Participant has received prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D. Participants who received prior treatment with a KRAS G12D inhibitor/degrader are eligible for the ASP3082 combination therapy cohort.
- Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention.
- Participant is expected to require another form of antineoplastic therapy while on study treatment.
- Participant has any condition which makes the participant unsuitable for study participation (such as psychiatric illness/social situations that would limit compliance with study requirements).
- Participant has had major surgery within 4 weeks prior to first dose of study intervention.
- For ASP3082 Combination Therapy:
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (53)
City of Hope National Medical Center
Duarte, California, 91010, United States
UCLA Santa Monica Hematology Oncology
Santa Monica, California, 90404, United States
Denver HealthONE Drug Development Unit
Denver, Colorado, 80218, United States
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, 06520-8028, United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
University of Florida, Davis Cancer Center
Gainesville, Florida, 32610, United States
Florida Cancer Specialist
Lake Mary, Florida, 32746, United States
Florida Cancer Specialists & Research Institute Sarasota
Sarasota, Florida, 34232-6422, United States
University of Kansas Medical Center
Westwood, Kansas, 66205, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Trinity Health Ann Arbor Hospital
Ypsilanti, Michigan, 48197, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Columbia University - Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Case Western
Cleveland, Ohio, 44106, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
SCRI Oncology Partners
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
NEXT Oncology
San Antonio, Texas, 78229, United States
NEXT Oncology - Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
University of Wisconsin Hospital
Madison, Wisconsin, 53792, United States
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Fudan University Shanghai Cancer Center
Xuhui District, Shanghai Municipality, China
Site FR33003
La Tronche, Grenobele, France
Site FR33002
Bordeaux, France
Site FR33001
Lyon, France
Site FR33005
Lyon, France
Site FR33004
Villejuif, Île-de-France Region, France
Aichi Cancer Center
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
Shikoku Cancer Center
Matsuyama, Ehime, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, Japan
Kindai University Hospital
Sayama, Osaka, Japan
Shizuoka Cancer Center
Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, Japan
Yamaguchi University Hospital
Ube, Yamaguchi, Japan
Osaka International Cancer Institute
Osaka, Japan
PanOncology Trials
San Juan, 00935, Puerto Rico
Site KR82005
Goyang-si, Gyeonggi-do, South Korea
Site KR82002
Seongnam-si, Gyeonggi-do, South Korea
Site KR82001
Jongno -Gu, Seoul, South Korea
Site KR82003
Seodaemun-gu, Seoul, South Korea
Site KR82004
Songpa-gu, Seoul, South Korea
Site ES34001
Barcelona, Spain
Site ES34004
Madrid, Spain
Site ES34002
Málaga, Spain
Site ES34003
Seville, Spain
Related Publications (1)
Park W, Kasi A, Spira AI, Paz-Ares Rodriguez L, Herzberg BO, Pelster MS, Tolcher AW, Kuboki Y, Kitano S, Shoji H, Wang JS, Berlin JD, Hollebecque A, LoRusso P, Fountzilas C, Cassier PA, Nishina T, Sakai D, Inagaki C, Morgensztern D, Ueno M, Jung M, Kim SW, Janne PA, Italiano A, You B, Macarulla T, Fujii H, Shetty A, Lu Y, Cui D, Kadam S, Gill SC, Toyoshima J, Saito T, Goldman JW. Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer. N Engl J Med. 2026 Mar 25. doi: 10.1056/NEJMoa2600752. Online ahead of print.
PMID: 41879829DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Inc
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 16, 2022
First Posted
May 19, 2022
Study Start
June 8, 2022
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
April 14, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.