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

Astellas

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor

Treatments: Drug: ASP4396

Study type: Interventional

Funder types: Industry

Identifiers

NCT06364696

4396-CL-0101

Details and patient eligibility

About

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.

Enrollment: 175 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

175 participants in 2 patient groups

ASP4396 Dose Escalation

Experimental group

Description:

Participants will receive ASP4396 in a 21-day cycle.

Treatment:

Drug: ASP4396

ASP4396 Dose Expansion

Experimental group

Description:

Participants will receive ASP4396 in a 21-day cycle.

Treatment:

Drug: ASP4396