Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 in Subjects with Advanced or Metastatic Solid Tumors

JRCT ID: jRCT2031220006

Registered date:08/04/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced or metastatic solid tumors with KRASG12C mutations
• Date of first enrollment: 01/05/2022
• Target sample size: 12
• Countries of recruitment: China,Japan
• Study type: Interventional
• Intervention(s): Every 21 day period will be considered as 1 treatment cycle. Subjects may continue daily D-1553 until disease progression, unacceptable treatment-related toxicity, withdrawal of consent or discontinuation for any reason, whichever occurs first.

Outcome(s)

Primary Outcome

- Type, incidence, severity (graded by NCI CTCAE, v5.0), attribution and timing of AEs;
- Incidence of DLTs.

Secondary Outcome

- PK parameters (AUC0-t, AUCinf, MRT, Cmax, tmax, Cmin, t1/2, Vdss/F and CL/F) of D-1553;
- ORR(CR + PR), DCR (CR+PR+SD), PFS and DOR, evaluated by RECIST, v1.1.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Regarding solid tumors in 4., currently only accepting patients with pancreatic cancer. (After April 12, 2023)

1.Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must have voluntarily signed and dated an IRB/IEC approved ICF that is in accordance with regulatory and ethics guidelines and it must be signed before the performance of any protocol related procedures or tests.
2.Subject is male or female of at least 20 years of age at the time of signing ICF.
3.Subject must be willing and able to comply with all scheduled visits, treatment, laboratory tests, be able to take oral medication and accept other requirements of the study.
4.Subject with histologically proven, locally advanced, unresectable and/or metastatic solid tumor.
5.Subject has KRASG12C mutation in tumor tissue, blood, pleural effusion or other samples containing cancer cells or DNA. Historical, local laboratory result (up to 5 years prior to signing ICF) can be used for subjects.
6.Subject has advanced or metastatic solid tumors for which no standard treatment is available or the subject is refractory to or intolerant of existing standard treatment.
7.Subject has measurable disease according to RECIST, v1.1. For Japan Safety Confirmation Portion, subjects with non-measurable lesion as per RECIST, v1.1. are also acceptable.
8.Subject has an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1.
9.Subject has adequate hematologic function, defined as:
- Platelet count = > 100*10^9/L
- Hemoglobin level = > 9.0 g/dL.
- Absolute neutrophil count (ANC) = > 1.5*10^9/L

*Please contact us for more details.

Exclude criteria

1. Subject has prior anticancer or investigational drug treatment as follows:
a. Prior treatment with an inhibitor specific to KRASG12C mutation, such as AMG510, MRTX849, LY3499446 and GDC-6036 (For Japan Safety Confirmation Portion, KRASG12C inhibitor-naive subjects and subjects who received prior KRASG12C inhibitors are eligible for the 600 mg BID cohort, whereas only subjects who received prior KRASG12C inhibitors are eligible for the 800 mg BID cohort);
Note: In Japan, treatment with KRAS G12C inhibitor therapy is approved in patient with KRAS G12C-mutation-positive irresectable advance or recurrent NSCLC who progressed after receiving prior system therapy. Therefore, patients who are qualified for approved KRAS G12C inhibitor therapy can only participate in this study after completion or discontinuation of approved treatment. However, patients who received other experimental KRASG12C inhibitors are eligible to participate in this study.
b. Any anticancer therapy (including chemotherapy, targeted therapy, immune therapy, or other investigational agents) or any other investigational drug therapy less than 14 days or 3 half-lives (whichever is shorter) prior to first dose of study intervention.
2. Subject with unstable or progressive central nervous system (CNS) metastases. Subjects with history of brain metastases are allowed for inclusion, if they are clinically stable. For subjects ever treated with corticosteroids, they must be off corticosteroids for at least 3 weeks prior to first dose of study intervention. For subjects on anti-seizure treatment, their medications must be on stable doses for at least 2 weeks. There should be no evidence of CNS progression prior to enrollment as confirmed by MRI with or without contrast MRI or CT (if MRI is not suitable). The brain MRI or CT should be performed at least 4 weeks after the last brain radiation, if any.
3. Subjects with clinically significant cardiovascular disease, including:
a. Subject with acute myocardial infarction, severe/unstable angina; or with cardiac insufficiency of New York Heart Association (NYHA) Functional Classification Grade 2 or above.
b. Subject has corrected QT interval using Fridericia's formula (QTcF) prolongation at rest, where the mean QTc interval is > 470 msec based on triplicate measurements of electrocardiogram (ECG).
c. Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death;
d. Clinically uncontrolled hypertension (after standard antihypertensive treatment, systolic blood pressure = > 150 mmHg and/or diastolic blood pressure = > 100 mmHg);

*Please contact us for more details.

Related Information

• Primary Sponsor: Kitano Tina