A Study of A166 in Patients With Advanced Solid Malignant Tumors

Kelun Pharmaceutical

Status and phase: Active, not recruiting; Phase 1

Conditions: Breast Cancer

Treatments: Drug: A166

Study type: Interventional

Funder types: Industry

Identifiers

NCT05311397

KL166-I-01-CTP

Details and patient eligibility

About

This is a single arm, open-label, dose-escalation and dose-expansion phase I study evaluating A166 in patients with HER2-expressing locally advanced or metastatic solid tumors.

Full description

The first stage will determine the recommended stage 2 dose (RS2D) in patients with unresectable, locally advanced or metastatic HER2-expressing solid tumors based on safety, tolerability, pharmacokinetic characteristics and antitumor activity. The second stage will assess the safety, tolerability, pharmacokinetic characteristics and antitumor activity in dose-expansion cohorts (RS2D:3.6 mg/kg, 4.8 mg/kg and 6.0 mg/kg dose groups).

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

The first stage（Dose-escalation）

Experimental group

Description:

According to the initial dose, the highest dose and the modified Fibonacci method, the dose escalation of A166 for injection is designed as: 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg (the highest dose is tentatively set at 4.8 mg/kg).

Treatment:

Drug: A166

The second stage（Dose-expansion）

Experimental group

Description:

The administered dose of A166 for injection is RS2D obtained in the first stage .

Treatment:

Drug: A166