Clinical trial NCT06364696: A Study to Find a Suitable Dose of ASP4396 in Adults With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Locally Advanced Solid Tumors
Metastatic Solid Tumors
ASP4396
KRAS G12D
Non-small Cell Lung Cancer
Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2024-04-15
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) for ASP4369
timeFrame: Up to 21 days
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 12 months
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 12 months
measure: Number of Participants with laboratory value abnormalities and/or AEs
timeFrame: Up to 12 months
measure: Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs
timeFrame: Up to 12 months
measure: Number of Participants with vital sign abnormalities and/or AEs
timeFrame: Up to 12 months
measure: Number of Participants with physical exam abnormalities and/or AEs
timeFrame: Up to 12 months
measure: Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status score
timeFrame: Up to 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to 12 months
measure: Duration of Response (DOR) per RECIST v 1.1
timeFrame: Up to 12 months
measure: Disease Control Rate (DCR) per RECIST v 1.1
timeFrame: Up to 12 months
measure: Progression Free Survival (PFS) per RECIST v1.1
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: Up to 12 months
measure: Pharmacokinetics (PK) of ASP4396 in plasma: area under the concentration-time curve from the time of dosing to 24 hours after dosing (AUC24h)
timeFrame: Up to 12 months
measure: PK of ASP4396 metabolite in plasma: AUC24h
timeFrame: Up to 12 months
measure: PK of ASP4396 in plasma: AUC168h
timeFrame: Up to 12 months
measure: PK of ASP4396 metabolite in plasma: AUC168h
timeFrame: Up to 12 months
measure: PK of ASP4396 in plasma: Maximum Concentration (Cmax)
timeFrame: Up to 12 months
measure: PK of ASP4396 metabolite in plasma: Cmax
timeFrame: Up to 12 months
measure: PK of ASP4396 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Up to 12 months
measure: PK of ASP4396 metabolite in plasma: Ctrough
timeFrame: Up to 12 months
measure: PK of ASP4396 in plasma: Time of maximum concentration (tmax)
timeFrame: Up to 12 months
measure: PK of ASP4396 metabolite in plasma: tmax
timeFrame: Up to 12 months
measure: Change from baseline of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D amino acid substitution (G12D) tumor samples
timeFrame: Baseline and up to 12 months
Other outcomes:
Locations:
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Irving
country: United States
facility: NEXT Oncology Dallas
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
Study officials:
affiliation: Astellas Pharma Inc
name: Central Contact
role: STUDY_DIRECTOR
References: