A Study to Find a Suitable Dose of ASP4396 in Adults With Solid Tumors

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06364696
• Other study ID #: 4396-CL-0101
• Status: Recruiting
• Phase: Phase 1
• Start date: April 16, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: April 2024
• Source: Astellas Pharma Inc
• Contact: Astellas Pharma Inc.
• Phone: 800-888-7704
• Email: Astellas.registration[@]astellas.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• ASP4396
Intravenous (IV) infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

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