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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
681
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
Intravenous Infusion
City of Hope National Medical Center
Duarte, California, United States
RECRUITINGUCLA Santa Monica Hematology Oncology
Santa Monica, California, United States
RECRUITINGDenver HealthONE Drug Development Unit
Denver, Colorado, United States
RECRUITINGSmilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, United States
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
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR is defined as the proportion of participants whose best overall response is rated as complete response (CR) or partial response (PR) per RECIST v1.1.
Time frame: Up to 48 months
Duration of Response (DOR) per RECIST v 1.1
DOR is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date of documented radiological disease progression per RECIST v1.1 or death in the absence of progression.
Time frame: Up to 48 months
Disease Control Rate (DCR) per RECIST v 1.1
DCR is defined as the proportion of participants whose best overall response is rated as CR, PR or SD based on RECIST v1.1.
Time frame: Up to 48 months
Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)
AUC will be recorded from the PK plasma samples collected.
Time frame: Up to 48 months
PK of ASP3082 in plasma: Maximum Concentration (Cmax)
Cmax will be recorded from the PK plasma samples collected.
Time frame: Up to 48 months
PK of ASP3082 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
Ctrough will be recorded from the PK plasma samples collected.
Time frame: Up to 48 months
PK of ASP3082 in plasma: Time of maximum concentration (tmax)
tmax will be recorded from the PK plasma samples collected.
Time frame: Up to 48 months
Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Georgetown University Hospital
Washington D.C., District of Columbia, United States
RECRUITINGUniversity of Florida, Davis Cancer Center
Gainesville, Florida, United States
RECRUITINGFlorida Cancer Specialist
Lake Mary, Florida, United States
RECRUITINGFlorida Cancer Specialists & Research Institute Sarasota
Sarasota, Florida, United States
RECRUITINGUniversity of Kansas Medical Center
Westwood, Kansas, United States
RECRUITINGBeth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITING...and 43 more locations
Changes in KRAS G12D in tumor samples will be measured.
Time frame: Up to 48 months