Evaluating A166 in Patients with Advanced Solid Tumors

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of A166 in Patients With Unresectable, Locally Advanced or Metastatic HER2-expressing Solid Tumors (KL166-I-01-CTP)

This study is testing a new treatment called A166 to see if it can help people with advanced solid tumors that express HER2 feel better and improve their condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. (Industry-sponsored)
• Drugs / interventions: trastuzumab, chemotherapy, immunotherapy, doxorubicin
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05311397 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label phase I study assessing the safety and efficacy of A166 in patients with HER2-expressing locally advanced or metastatic solid tumors. The study consists of two stages: the first stage focuses on determining the recommended stage 2 dose based on safety, tolerability, pharmacokinetics, and antitumor activity. The second stage involves dose-expansion cohorts to further evaluate these parameters at specified dose levels.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed incurable locally advanced or metastatic HER2-positive solid tumors.

Not a fit: Patients with tumors that are not HER2-positive or those who can benefit from existing standard treatments may not receive benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced HER2-positive solid tumors who have limited alternatives.

How similar studies have performed: Other studies targeting HER2-positive tumors have shown promising results, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign informed consent form;
2. Age ≥ 18 years old, no gender limit;
3. Patients had a histologically confirmed incurable locally advanced or metastatic solid tumors;
4. Determined HER2-positive disease (detected by ISH or NGS) or HER2-expressing disease by evaluation or detection. Definition of HER2 expression in this study: Immunohistochemistry \[IHC\] ≥ 1＋;
5. Patients unable to benefit from the available standard treatment according to the judgment of the investigator;
6. White blood cell count (WBC) ≥ 4.0×109/L or ≥ lower limit of normal value; Neutrophil count (NEUT) ≥ 1.5×109/L; Platelet count (PLT) ≥ 100×109/L; Hemoglobin concentration ≥ 9.0 g/dL;
7. Total bilirubin (TBIL) ≤ 1.5×ULN. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN). For patients with liver metastases, ALT and AST ≤ 5 times ULN, and for patients with liver and/or bone metastases, alkaline phosphatase ≤ 5 times ULN;
8. Creatinine clearance rate ≥ 50 ml/min;
9. Patients had an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1, the expected survival time is ≥ 3 months;
10. During the study period and within 7 months after the final administration of A166, patients with fertility (regardless of male and female) must receive effective medical contraceptive measures;
11. The patients must recover from all acute toxicities of the previous treatment (relieved to grade 1 or baseline), except for hair loss and vitiligo;

Exclusion Criteria:

1. Severe or uncontrollable heart disease requiring treatment, or grade 3 or 4 congestive heart failure according to the New York Society of Cardiology (NYHA), or unstable angina pectoris that cannot be controlled by drugs, or history of myocardial infarction within 6 months prior to enrollment, or severe arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia);
2. History of ≥ Grade 3 allergic reaction to trastuzumab;
3. Permanent with drawal of trastuzumab due to any previous toxicity;
4. Patients with brain metastases who have symptoms or who have received the radiotherapy or surgery within 3 months before the first administration;
5. Patients requiring oxygen therapy in daily activities;
6. Grade 2 or higher peripheral neuropathy;
7. Any chemotherapy, hormone therapy (except dexamethasone), radiotherapy, immunotherapy or biological therapy received within 4 weeks before the first administration;
8. Prior-treatment with other clinical research drugs within 4 weeks before the first administration;
9. Patients who have undergone major surgery within 4 weeks before the first administration;
10. Active hepatitis B (hepatitis B surface antigen positive and HBV-DNA higher than the upper limit of reference value) or hepatitis C (positive hepatitis C virus antibody and HCV-RNA higher than the upper limit of reference value); current or past alcoholics ; Liver cirrhosis;
11. Known active human immunodeficiency virus (HIV);
12. Systemic diseases that cannot be controlled, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, glaucoma, etc according to investigator's judgment;
13. Current pregnancy or lactation;
14. QTc interval\> 470 ms according to the baseline measurement:;
15. Left ventricular ejection fraction (LVEF) \<45% according to the echocardiogram (ECHO) or multi-gate circuit controlled acquisition (MUGA) ;
16. Previous cumulative doxorubicin accumulation \> 360 mg/m2 or its equivalent dose;

Where this trial is running

Shanghai, Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)

Conditions Breast Cancer