IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor

NCT05814536 | Terminated Phase 1

• 1 other identifier: AB-218-G104
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 14

Brief Summary

This is an open label, single-arm Phase I study to evaluate the safety, tolerability, PK and preliminary efficacy of AB-218, an oral IDH1 inhibitor, for the treatment of adult patients with advanced IDH1 mutant cholangiocarcinoma and other solid tumors who have failed at least one prior therapy in the advanced stage. The study contains a dose escalation part and a dose expansion part. In the dose escalation part, participants are enrolled sequentially into one of 3 dose levels of AB-218 (125 mg BID, 250 mg BID and 500 mg BID) following a 3+3 rule. Intensive PK sampling will be performed during the dose escalation part. Participants will be followed up for DLTs from the date of first study dose to 28 days afterwards. When all participants in the dose escalation part have completed the 28-day DLT observation period, SMC will review the available data including but not limited to safety, tolerability and PK, and then recommend the dose for the study dose expansion part. In the dose expansion part, there are 2 disease cohorts planned: cholangiocarcinoma (CCA) and other IDH1 mutant solid tumors. It is planned to enrol 30 participants in the CCA cohort and another 15 participants in other IDH1 mutant solid tumors, to assess the safety and preliminary efficacy of AB-218. Sparse PK samples will be collected to further evaluate the PK profile in the different target populations. Each participant will undergo screening up to 28 days prior to the start of the treatment period. The treatment period consists of a visit on Day 1 of every 28-day cycle and continues until any of disease progression, unacceptable toxicity, withdrawal of consent or death. An end of treatment (or early discontinuation) visit occurs 30 days (± 7 days) after the last dose of study medication, and a survival follow call every 12 weeks until death, withdrawal of informed consent, loss to follow-up (LTFU) or termination of the study by the sponsor, whichever occurs first.

Conditions

Cholangiocarcinoma With IDH1 Mutation; Solid Tumors With IDH1 Mutation

Outcome Measures

Primary Outcomes (2)

• TEAEs

  Treatment-Emergent Adverse Events (TEAEs) including events reported following physical examination, vital signs assessment, clinical laboratory assessment or electrocardiogram (ECG)

  About 24 months

• DLT incidence

  Dose limiting toxicity incidence

  Dose escalation part, about 6 months

Secondary Outcomes (12)

• Overall Response Rate

  About 24 months

• Duration of Response

  About 24 months

• Disease Control Rate

  About 24 months

• Progress Free Survival

  About 24 months

• Overall Survival

  About 48 months

Study Arms (1)

AB-218

EXPERIMENTAL

AB-218 for the treatment of adult patients with advanced cholangiocarcinoma, chondrosarcoma and other solid tumors with IDH1 mutation.

Drug: AB-218 capsule

Interventions

AB-218 capsule DRUG

Take AB-218 orally twice daily, ideally with 12 hours between doses (and a minimum of 8 hours between doses), at a dose assigned by the study. The study treatment is defined as occurring in 28-day cycles with continuous dosing. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs earlier.

AB-218

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be ≥18 years of age at the time of signing the informed consent form.
• Must have locally advanced or metastatic solid tumors that have recurred or progressed following treatment with at least 1 prior systemic therapy, or that have not responded to prior systemic therapy; or the patient is unfit for any intensive chemotherapy in the first line setting.
• Must have histologically confirmed IDH1 mutation from testing of a primary or metastatic tumor before first study treatment. Patients must have archival primary tumor biopsy or surgical specimens, or biopsies of recurrence of metastasis for IDH1 mutation confirmation and status of other concurrent gene mutations. Patients shall provide formalin-fixed paraffin-embedded (FFPE) tissue slides without staining, which are shipped to the designated laboratory. The IDH1 mutation must be determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Patients whose tumors have not been tested for IDH1 mutation, must be consented with the pre-screening ICF to allow collection of tumor tissue and testing at the designated qualified central laboratory. These patients may only be consented to the study with the full ICF if they have a documented IDH1 mutation.
• Must have a measurable lesion(s) as per the RECIST v1.1 criteria.
• Patients with chronic HCV infection are acceptable to enroll, if ≥ 4 weeks between achieving sustained viral response and start of study drug. Anti-viral therapy is allowed during the study treatment period.
• Patients with chronic HBV infection may enroll in the study, if HBV DNA is \<1000 copies/mL prior to the start of study treatment. Anti-viral therapy is allowed during the study treatment period.
• Must have life expectancy ≥ 3 months.
• Must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤ 1.
• Must have a Child-Pugh class A liver score within 7 days prior to first dose of study treatment.
• Must have adequate organ functions as defined below:
• Absolute neutrophil count (ANC)≥ 1.5 X 109/L, Hemoglobin≥ 80 g/L Creatinine Clearance\* (Cockcroft-Gault Formula) ≥ 60 mL/min Total Bilirubin≤ 2 x ULN,≤ 3 x ULN, for participants with documented Gilbert's syndrome AST and ALT≤ 5 x ULN, Albumin≥ 30 g/L, INR ≤ 1.5 x ULN unless patient is receiving anti-coagulant therapy, aPTT must be within the therapeutic range of intended use of anticoagulants
• Adequate biliary drainage, with no evidence of ongoing infection (patients on maintenance antibiotics are eligible when acute sepsis has resolved)
• Recovery to Grade 1 from any toxicities due to prior therapies, except conditions such as peripheral neuropathy, alopecia and irreversible changes associated with radiation therapy; peripheral neuropathy due to prior therapies must have recovered to ≤ Grade 2.
• Female patients who engage in heterosexual intercourse must be of nonchildbearing potential, defined as either surgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR be postmenopausal with at least 1 year of amenorrhea, OR must agree to use a highly effective method of contraception from the beginning of Screening until at least 90 days after the last dose of study drug.
• Acceptable highly effective methods of contraception include:

You may not qualify if:

• Patients diagnosed with IDH1 mutant glioma or acute myeloid leukemia (AML).
• Patients with history or complication of any of the following diseases within 3 months prior to the initial dose of the investigational drug.
• Myocardial infarction
• Severe or unstable angina pectoris
• Coronary or peripheral endovascular treatment
• Heart failure
• Cerebrovascular disorder including transient ischemic attack, stroke, central nervous system (CNS) bleeding.
• Uncontrolled active systemic fungal, bacterial, or other infection (despite appropriate antibiotics or other treatment).
• HIV infection as determined by an HIV antibody test.
• Presence of Grade 3 ascites, as defined in the Guidance on the Management of Ascites and Complications in Cirrhosis 36. The patient has significant bloating, tests positive for shifting dullness, and may have abdominal distension leading to umbilical hernia; on assessment with ultrasound, the ascites occupies the entire abdominal cavity, and the middle abdomen is filled with ascites, with a depth of \>10 cm.
• Gastrointestinal diseases that may interfere with oral ingestion of the study drug or may affect absorption of the study drug.
• Prior anticancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• Systematic Therapy: within 3 weeks
• Radical Surgery: within 3 weeks
• Radiation therapy: within 12 weeks (excluding the palliative radiotherapy or radiotherapy on the non-target lesions)

Sponsors & Collaborators

• AnHeart Therapeutics Inc.: lead

Study Sites (14)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100730, China

Location

Beijing Jishuitan Hospital

Beijing, Beijing Municipality, China

Location

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

The fourth hospital of Hebei medical university

Shijiazhuang, Hebei, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Liaoning Cancer Hospital

Shenyang, Liaoning, China

Location

Shandong Cancer Hospital

Jinan, Shandong, China

Location

Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, China

Location

The Third Affiliated Hospital of the PLA naval medical university

Shanghai, Shanghai Municipality, China

Location

Shulan (Hangzhou) Hospital

Hangzhou, Zhejiang, China

Location

Jinan Central Hospital

Jinan, Zhejiang, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 18, 2023
• Study Start: May 6, 2023
• Primary Completion: August 15, 2024
• Study Completion: August 15, 2024
• Last Updated: October 18, 2024

Record last verified: 2024-10

Locations

CN (14)