A Study of AK-1286 in Patients With Advanced Solid Tumors

Official title

A Phase 1,Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of AK-1286 in Patients With Advanced Solid Tumors

Overview

This is a phase 1 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of AK-1286 in patients with advanced solid tumors, so as to confirm the recommended phase 2 dose of AK-1286 and obtain the preliminary efficacy information of patients with advanced solid tumors.

Interventions

• Drug AK-1286
  Cohort 1: 1 mg/d QD AK-1286 PO,DLT observation period: 21 days. Cohort 2: 2 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 3: 4 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 4: 5 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 5: 16 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 6: 24 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 7: 36 mg/d BID AK-1286 PO,DLT observation period: 21 days. Cohort 8: 50 mg/d BID AK-1286 PO,DLT observ

Primary outcome measures

• Occurrence of drug limited toxicities (DLTs) [Time frame: From Time of First dose through DLT observation period, 21 days]
• Incidence of Treatment-emergent adverse event (TEAEs) and serious adverse events (SAEs) [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Number of patients with changes in laboratory parameters from baseline [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Number of participants with changes in clinically significant vital sign from baseline [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]

Secondary outcome measures (4)

• The overall response rate (ORR) [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Progression free survival（PFS） [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Overall survival（OS） [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Disease control rate（DCR） [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]

Eligibility criteria

Inclusion criteria

• Age 18-75 years (including cut-off value), gender is not limited;
• Patients with histologically or cytologically diagnosed advanced malignant solid tumors who have failed or are unable to tolerate standard treatment regimens with systemic standard therapy.
• participants in the dose expansion phase must have quantifiable lesions according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
• Anticipated minimum survival duration of 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participants must meet the laboratory criteria.A. Bone marrow function needs to meet#ANC≥1.5×109/L#PLT≥100×109/L#Hb≥9g/dL B. renal function#Cr≤1.5 times the upper limit of normal value#or Creatinine clearance≥50ml/min C. liver function#total bilirubin<1.5 x ULN#For subjects with documented Gilbert syndrome,< 2.0 x ULN or subjects with indirect bilirubin levels suggesting a source of extrahepatic elevation<3.0 x ULN#ALT and AST≤ 2.5 x ULN#If liver metastasis occurs≤ 5 x ULN#D. Coagulation function#Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x upper normal limit (ULN), or international normalized ratio (INR) < 1.5 or within the target range (if preventive anticoagulant therapy is performed# E). The corrected QT interval (QTcF) of Fridericia method is less than 450 ms for males and less than 470 ms for females.
• The elution period of macromolecular drugs is ≥ 4 weeks, and that of oral fluorouracil and small molecule targeted drugs is ≥ 2 weeks
• Fertile women must have a negative blood pregnancy test within 7 days before receiving the first study drug;
• For fertile men and women, they must be willing to use appropriate contraceptive methods 30 days before the first study drug administration and 120 days after the last study drug administration;
• Did not participate in the clinical trial as a subject within 1 month before participating in the trial;
• According to the judgment of the researcher, the compliance is high,willing to complete the test and can abide by the test scheme;
• Voluntarily participate in this clinical trial, understand the research procedures and be able to sign the informed consent form in writing.

Exclusion criteria

• Untreated patients with brain metastasis
• Other malignant tumors in recent five years. Basal cell carcinoma of the skin, except squamous cell carcinoma of the skin or cervical carcinoma in situ after potential treatment;
• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association > grade II), unstable angina pectoris or arrhythmia requiring drug treatment occurred within 6 months before enrollment;
• Have a history of gastrointestinal diseases or gastric surgery or inability to swallow oral drugs;
• Active infection requiring treatment;
• Patients with active hepatitis B (hepatitis B surface antigen and / or hepatitis B core antibody positive and HBV-DNA > 103 copies /mL or 200IU/mL) or hepatitis C patients (hepatitis C virus positive and / or HCV-RNA positive) or HIV positive patients are required to receive treatment.
• Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first use of the study drug, or elective surgery during the trial, or therapeutic or palliative radiotherapy within 2 weeks before the first use of the study drug;
• Allergic constitution, or known history of allergy to this drug component;
• According to the researchers' judgement, there are serious diseases that may endanger the safety of patients or affect the completion of research, such as uncontrollable hypertension, uncontrollable diabetes and thyroid diseases.
• There is fluid accumulation in the third space that cannot be controlled by drainage or other methods (such as massive identification and hydrothorax)
• Have a clear history of neurological or mental disorders；
• The researchers believe that the subjects are not suitable to participate in this study for other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06779045 · AK-1286-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗