Solid Tumor Clinical Trial
Official title:
An Open-label Phase 1 Study of ASP4396 in Participants With Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation
Genes contain genetic code which tell the body which proteins to make. Some 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. The so-called G12D mutation in the KRAS gene is common in people with some solid tumors. ASP4396 is being developed as a potential new treatment for solid tumors in people who have the G12D mutation in their KRAS gene. ASP4396 is not currently available as a treatment for the public. In this study, researchers will learn how ASP4396 is processed by and acts upon the body. This information will help find a suitable dose and to check for potential medical problems from ASP4396. In this study, ASP4396 is being given to humans for the first time. People in this study will be adults with locally advanced (unresectable), or metastatic solid tumors 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 may have been previously treated with standard therapies or refused to receive those treatments. The main aims of the study are to check the safety of ASP4396, how well people cope with medical problems during the study (how well it is tolerated), and to find a suitable dose of ASP4396. This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP4396. 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 ASP4396. For each dose, all medical problems will be recorded. The first group will receive the lowest dose of ASP4396. A medical expert panel will check the results and decide if the next group can receive a higher dose of ASP4396. The panel will do this until all groups have taken ASP4396 or until suitable doses have been selected for Part 2. Part 2 is called Dose Expansion. Other different small groups of people will receive ASP4396 with the most suitable doses worked out from Part 1. This will help find a more accurate dose of ASP4396 to use in future studies. In both parts of the study, ASP4396 will be given through a vein. This is called an infusion. Each treatment cycle is 21 days long. People will continue treatment until: they have medical problems from the treatment they can't cope with (can't tolerate); their cancer gets worse; they start other cancer treatment; or they ask to stop treatment. People will visit the clinic on certain days during their treatment, with extra visits during the first 2 cycles of treatment. The study doctors will check for any medical problems from ASP4396. Also, people in the study will have a health check including blood tests. 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 treatment with the option of a tumor sample being taken after treatment has finished. People will visit the clinic about 7 days after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. After this, people will visit the clinic for a health check several times. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not. After treatment has finished, people in the study will be followed up for up to 45 weeks.
Status | Recruiting |
Enrollment | 175 |
Est. completion date | April 30, 2027 |
Est. primary completion date | April 30, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented KRAS G12D mutation and has received prior standard therapy. - Participant has at least 1 measurable lesion per RECIST v1.1. - Participant has an ECOG performance status of 0 or 1. - Participant has adequate organ function. Exclusion Criteria: - Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic and treated and stable CNS metastases are eligible. - Participant has leptomeningeal disease as a manifestation of the current malignancy. - Participant has another prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years different from the primary malignancy for this study, 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 with active hepatitis B or hepatitis C virus (HCV). - Participant has a known history of human immunodeficiency virus (HIV) infection with acquired immunodeficiency syndrome (AIDS)-related complications. - Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention. - Participant is expected to require another form of anticancer therapy while on study intervention. - Participant has any condition that makes the participant unsuitable for study participation. |
Country | Name | City | State |
---|---|---|---|
United States | NEXT Oncology Virginia | Fairfax | Virginia |
United States | START Midwest | Grand Rapids | Michigan |
United States | NEXT Oncology Dallas | Irving | Texas |
United States | START Mountain Region | West Valley City | Utah |
Lead Sponsor | Collaborator |
---|---|
Astellas Pharma Inc |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of Dose Limiting Toxicities (DLTs) for ASP4369 | A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 at least possibly related to study intervention. | Up to 21 days | |
Primary | 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 intervention, whether or not considered related to the study intervention. | Up to 12 months | |
Primary | 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 12 months | |
Primary | Number of Participants with laboratory value abnormalities and/or AEs | Number of participants with potentially clinically significant laboratory values. | Up to 12 months | |
Primary | Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs | Number of participants with potentially clinically significant ECG values. | Up to 12 months | |
Primary | Number of Participants with vital sign abnormalities and/or AEs | Number of participants with potentially clinically significant vital sign values. | Up to 12 months | |
Primary | Number of Participants with physical exam abnormalities and/or AEs | Number of participants with potentially clinically significant physical exam values or symptoms. | Up to 12 months | |
Primary | Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status score | 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 12 months | |
Secondary | 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 with confirmation status is rated as (confirmed or unconfirmed) complete response (CR) or (confirmed or unconfirmed) partial response (PR) based on RECIST v1.1. | Up to 12 months | |
Secondary | Duration of Response (DOR) per RECIST v 1.1 | DOR is measured from the day the criteria are first met for time point overall response rated as CR or 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. | Up to 12 months | |
Secondary | Disease Control Rate (DCR) per RECIST v 1.1 | DCR is defined as the proportion of participants whose best overall response with confirmation status is rated as (confirmed or unconfirmed) CR, (confirmed or unconfirmed) PR or stable disease (SD) (including non-CR/non-progressive disease [PD] for participants with no measurable disease at baseline) based on RECIST v1.1. | Up to 12 months | |
Secondary | Progression Free Survival (PFS) per RECIST v1.1 | PFS is defined as the time from the start of study intervention until the date of documented radiological disease progression per RECIST v1.1 or until death for any cause, whichever comes first. | Up to 12 months | |
Secondary | Overall Survival (OS) | OS is defined as the time from the start of study intervention until death due to any cause. | Up to 12 months | |
Secondary | Pharmacokinetics (PK) of ASP4396 in plasma: area under the concentration-time curve from the time of dosing to 24 hours after dosing (AUC24h) | AUC24h will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 metabolite in plasma: AUC24h | AUC24h will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 in plasma: AUC168h | AUC168h will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 metabolite in plasma: AUC168h | AUC168h will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 in plasma: Maximum Concentration (Cmax) | Cmax will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 metabolite in plasma: Cmax | Cmax will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough) | Ctrough will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 metabolite in plasma: Ctrough | Ctrough will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 in plasma: Time of maximum concentration (tmax) | tmax will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | PK of ASP4396 metabolite in plasma: tmax | tmax will be recorded from the PK plasma samples collected. | Up to 12 months | |
Secondary | Change from baseline of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D amino acid substitution (G12D) tumor samples | Changes in KRAS G12D in tumor samples will be measured. | Baseline and up to 12 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05691608 -
MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification 2
|
N/A | |
Recruiting |
NCT05580991 -
Intratumoral CAN1012(Selective TLR7 Agonist) in Subjects With Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT02846038 -
Understanding Communication in Healthcare to Achieve Trust (U-CHAT)
|
||
Recruiting |
NCT05159388 -
A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03181854 -
Randomized Controlled Trial of Integrated Early Palliative Care
|
N/A | |
Recruiting |
NCT06014502 -
Study to Evaluate IMGS-001 Treatment in Patients With Relapsed or Refractory Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05981703 -
A Study Investigating BGB-26808 Alone or in Combination With Tislelizumab in Participants With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04107311 -
Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients
|
||
Active, not recruiting |
NCT04078152 -
Durvalumab Long-Term Safety and Efficacy Study
|
Phase 4 | |
Completed |
NCT02250157 -
A Dose-regimen Finding Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oratecan in Subjects With Advanced Malignancies
|
Phase 1 | |
Recruiting |
NCT05566574 -
A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT03943004 -
Trial of DFP-14927 in Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT06036836 -
Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)
|
Phase 2 | |
Recruiting |
NCT05525858 -
KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
|
||
Recruiting |
NCT05798546 -
Treatment of Advanced Solid Tumors With Neo-T(GI-NeoT-02)
|
Phase 1 | |
Terminated |
NCT04586335 -
Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.
|
Phase 1 | |
Active, not recruiting |
NCT00479128 -
Bortezomib With Gemcitabine/Doxorubicin in Patients With Urothelial Cancer and Other Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04143789 -
Evaluation of AP-002 in Patients With Solid Tumors
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT04550663 -
NKG2D CAR-T(KD-025) in the Treatment of Relapsed or Refractory NKG2DL+ Tumors
|
Phase 1 | |
Completed |
NCT03980041 -
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
|
Phase 2 |