A Phase 1 Study of ASP3082 in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation
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.
Arms & interventions
- DrugSetidegrasib
Intravenous Infusion
- DrugCetuximab
Intravenous Infusion
- DrugLeucovorin
Intravenous Infusion
- DrugOxaliplatin
Intravenous Infusion
- DrugFluorouracil
Intravenous Infusion
- DrugIrinotecan
Intravenous Infusion
- DrugNanoparticle albumin-bound-paclitaxel
Intravenous Infusion
- DrugGemcitabine
Intravenous Infusion
- DrugDocetaxel
Intravenous Infusion
- DrugPembrolizumab
Intravenous Infusion
- DrugCisplatin
Intravenous Infusion
- DrugCarboplatin
Intravenous Infusion
- DrugPemetrexed
Intravenous Infusion
- DrugLiposomal Irinotecan
Intravenous Infusion
Outcome measures
Primary
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 48 months
Secondary
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to 48 months
Duration of Response (DOR) per RECIST v 1.1
Time frame: Up to 48 months
Disease Control Rate (DCR) per RECIST v 1.1
Time frame: Up to 48 months
Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)
Time frame: Up to 48 months
PK of ASP3082 in plasma: Maximum Concentration (Cmax)
Time frame: Up to 48 months
PK of ASP3082 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
Time frame: Up to 48 months
PK of ASP3082 in plasma: Time of maximum concentration (tmax)
Time frame: Up to 48 months
Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples
Time frame: Up to 48 months
Eligibility criteria
Study locations (23)
City of Hope National Medical Center
Duarte, California, 91010
UCLA Santa Monica Hematology Oncology
Santa Monica, California, 90404
Denver HealthONE Drug Development Unit
Denver, Colorado, 80218
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, 06520-8028
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
University of Florida, Davis Cancer Center
Gainesville, Florida, 32610
Florida Cancer Specialist
Lake Mary, Florida, 32746
Florida Cancer Specialists & Research Institute Sarasota
Sarasota, Florida, 34232-6422
University of Kansas Medical Center
Westwood, Kansas, 66205
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Trinity Health Ann Arbor Hospital
Ypsilanti, Michigan, 48197
Washington University School of Medicine
St Louis, Missouri, 63110
Roswell Park Cancer Institute
Buffalo, New York, 14263
Columbia University - Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Case Western
Cleveland, Ohio, 44106
Oregon Health and Science University
Portland, Oregon, 97239
SCRI Oncology Partners
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
NEXT Oncology
San Antonio, Texas, 78229
NEXT Oncology - Virginia Cancer Specialists
Fairfax, Virginia, 22031
University of Wisconsin Hospital
Madison, Wisconsin, 53792
References
- 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 Apr 9;394(14):1409-1420. doi: 10.1056/NEJMoa2600752. Epub 2026 Mar 25.(PubMed)