A Phase 1 Study of ASP5834 in Participants With Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies With KRAS Mutations or KRAS Amplifications
Summary
Genes contain genetic code which tell the body which proteins to make. Many types of cancer are caused by changes, or mutations, in a gene called KRAS. Researchers are looking for ways to stop the actions of abnormal proteins made from the mutated KRAS gene. ASP5834 is being studied in people with solid tumors who have certain KRAS gene mutations. Some people with solid tumors of the colon or rectum (colorectal cancer), will be given ASP5834 with panitumumab. Panitumumab is a treatment for colorectal cancer. In this study, the researchers will learn how ASP5834 is processed by and acts upon the body. This information will help find a suitable dose of ASP5834 and check for any potential medical problems from the treatment. The main aims of this study are to check the safety of ASP5834 given by itself or given with panitumumab, and how well it is tolerated; and to find a suitable dose of ASP5834 given by itself or given with panitumumab. People in this study will be adults with locally advanced, unresectable, or metastatic solid tumors with certain KRAS gene mutations. 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 either haven't responded to standard treatment or couldn't be given standard treatment. The key reasons people cannot take part are if they have specific uncontrollable cancers such as symptomatic or untreated cancers in nervous system, have specific heart conditions, swelling and irritation of lung tissues (pneumonitis or interstitial lung disease, also called ILD), infections, or have recently had a stroke or a bleed on the brain. In this study, ASP5834 is being given to humans for the first time. This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP5834 by itself or ASP5834 with panitumumab. This study will be in 2 parts: Part 1 is called Dose Escalation. Different small groups of people will receive lower to higher doses of either: ASP5834 by itself or ASP5834 with panitumumab. Only people who have colorectal cancer will receive ASP5834 with panitumumab. People with any type of solid tumor will receive ASP5834 by itself. For each dose, all medical problems will be recorded. A medical expert panel will check the results and decide if the next group can receive a higher dose of ASP5834. The panel will do this until the planned maximum number of people are treated or until suitable doses have been selected for Part 2. Part 2 is called Dose Expansion. Other different small groups of people will receive ASP5834 or ASP5834 with panitumumab. They will receive the most suitable doses worked out from Part 1. In both parts of the study, the study treatments ASP5834 and panitumumab will be given through a vein. This is called an infusion. Each study treatment cycle is either 21 days or 28 days long. People will continue study treatment until: they have medical problems from the study treatment they can't tolerate; their cancer gets worse; they start other cancer treatment; or they ask to stop study treatment. People will visit the clinic on certain days during their study treatment, with extra visits during the first 2 cycles of study treatment. The study doctors will check for any medical problems from ASP5834. Also, people in the study will have a health check. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken at certain visits during study treatment with the option of a tumor sample being taken if people's cancer gets worse or the cancer comes back. People will visit the clinic shortly after stopping treatment for a health check. After this, people will have health checks every couple of months to check the condition of their cancer. The number of visits and checks done will depend on the health of each person and whether they completed their study treatment or not. It is expected that people will be in this study for about 1 year.
Arms & interventions
- DrugASP5834
Intravenous infusion
- Drugpanitumumab
Intravenous infusion
Outcome measures
Primary
Incidence of Dose Limiting Toxicities (DLTs) (Dose Escalation only)
A DLT is defined as any Adverse Event (AE) which meets DLT criteria, not clearly due to the underlying disease or extraneous causes, that occurs within the DLT observation period.
Time frame: Up to 21 days
Number of participants with Adverse Events (AEs)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.
Time frame: Up to 40 months
Number of Participants with Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that at any dose either 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 or other medical situation.
Time frame: Up to 40 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 40 months
Number of Participants with Eye Exam abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant eye exam values.
Time frame: Up to 39 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 39 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 40 months
Number of participants with echocardiogram (ECHO) abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant ECHO values.
Time frame: Up to 39 months
Number of participants with multigated acquisition (MUGA) abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant MUGA values.
Time frame: Up to 39 months
Number of Participants with Physical Examination (PE) abnormalities and/or AEs
Number of participants with potentially clinically significant PE values.
Time frame: Up to 40 months
Number of Participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores
The ECOG scale will be used to assess performance status. Scores range from 0 (fully active) to 5 (dead). Negative change scores represent an improvement. Positive scores represent a decline in performance.
Time frame: Up to 40 months
Secondary
Objective Response Rate (ORR) of ASP5834 per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to 45 months
Duration of Response (DOR) of ASP5834 per RECIST v1.1
Time frame: Up to 45 months
Disease Control Rate (DCR) of ASP5834 per RECIST v1.1
Time frame: Up to 45 months
Progression Free Survival (PFS) per RECIST v1.1
Time frame: Up to 45 months
Overall Survival (OS)
Time frame: Up to 45 months
Pharmacokinetics (PK) of ASP5834 in plasma: area under the concentration-time curve at 24 hours (AUC24h)
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: area under the concentration-time curve at 168 hours (AUC168h)
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: area under the concentration-time curve at 336 hours (AUC336h) for 1 of 2 dose regimens
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: maximum concentration (Cmax)
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: trough concentration (Ctrough)
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: terminal elimination half-life (t1/2)
Time frame: Up to 39 months
Pharmacokinetics (PK) of ASP5834 in plasma: time of maximum concentration (tmax)
Time frame: Up to 39 months
Change from baseline in Kirsten rat sarcoma viral oncogene homolog (KRAS) protein levels
Time frame: Up to 45 months
Eligibility criteria
Study locations (11)
UCLA Santa Monica Hematology Oncology
Santa Monica, California, 90404
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322
Ochsner Health
Jefferson, Louisiana, 70121
START Midwest
Grand Rapids, Michigan, 49546
Washington University School of Medicine
St Louis, Missouri, 63110
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Roswell Cancer Institute
Buffalo, New York, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University Hospitals - UH Cleveland Medical Center
Cleveland, Ohio, 44106
NEXT Oncology Dallas
Irving, Texas, 75039
NEXT Oncology Virginia
Fairfax, Virginia, 22031