A Study of DXC006 in Patients With Advanced Solid Tumors and Hematologic Malignancies

Официальное название

An Open-label Dose Escalation and Cohort Expansion Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and and Efficacy of DXC006 in Patients With Advanced Solid Tumors and Hematologic Malignancies

Обзор

This is a phase I, open-label, first-in-human clinical study designed to evaluate the safety, tolerability, MTD, DLT, RP2D, the PK characteristics, preliminary anti-tumor activity, the immunogenicity of DXC006 in patients with a variety of solid tumors, including small cell lung cancer, multiple myeloma, and neuroblastoma, and hematological malignancies.

Подробное описание

This is a phase I, open-label, first-in-human clinical study designed to evaluate the safety, tolerability, MTD, DLT, RP2D, the PK characteristics, preliminary anti-tumor activity, the immunogenicity of DXC006 in patients with a variety of solid tumors, including small cell lung cancer, multiple myeloma, and neuroblastoma, and hematological. malignancies.

Вмешательства

• Препарат DXC006
  Dose escalation period: DXC006 is administered intravenously every two weeks (Q2W) at the dose corresponding to the enrolled dose cohort. Dose expansion period: DXC006 is administered intravenously Q2W at the corresponding dose.

Первичные конечные точки

• Number of participants that experienced dose limiting toxicities(DLTs) at given dose level. [Срок оценки: 28 days]
• Number of participants with adverse events (AEs) [Срок оценки: After first infusion of study drug, Through study completion an average of 1 year]

Вторичные конечные точки (12)

• Maximum observed serum or plasma concentration (Cmax) [Срок оценки: Through study completion an average of 1 year]
• Maximum serum drug time（Tmax） [Срок оценки: Through study completion an average of 1 year]
• Apparent volume of distribution(Vd) [Срок оценки: Through study completion an average of 1 year]
• Volume of distribution at steady state (Vss) [Срок оценки: Through study completion an average of 1 year]
• Terminal phase elimination half life (t½) [Срок оценки: Through study completion an average of 1 year]
• Area under the serum or plasma concentration time curve from 0 to the last measurable point (AUC0-t) [Срок оценки: Through study completion an average of 1 year]
• Area under the serum or plasma concentration time curve from 0 to infinity (AUC0-inf) [Срок оценки: Through study completion an average of 1 year]
• Clearance (CL) [Срок оценки: Through study completion an average of 1 year]
• Anti-drug antibodies (ADA) [Срок оценки: Through study completion an average of 1 year]
• Objective Response Rate (ORR) [Срок оценки: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year]
• Duration of response (DOR) [Срок оценки: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year]
• Progression Free Survival (PFS) [Срок оценки: om date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year]

Критерии участия

Критерии включения

• The patient voluntarily signed the informed consent form and followed the protocol requirements.
• Gender is not limited.
• Age ≥ 18 years old.
• Expected survival time ≥ 3 months.
• The Eastern Cooperative Oncology Group (ECOG) score 0-2.
• Subjects may provide biopsy or archival tumor tissue samples for the central laboratory to confirm expression levels of Target protein.
• Patients with solid tumors or hematologic tumors who have failed standard therapy, including small cell lung cancer, multiple myeloma, neuroblastoma, etc..
• Patients who have received ASCT treatment must meet the following conditions:

• ASCT > 100 days from start of study treatment.
• no active infection.
• Toxicity from prior antineoplastic therapy has recovered to Grade ≤ 1 (except alopecia) as defined by NCI-CTCAE v5.0, including peripheral neuropathy ≤ Grade 2.
• Organ function must meet the following requirements: blood routine:

(1) Patients with multiple myeloma: absolute neutrophil count (ANC) ≥ 1.0×109/L (previous use of granulocyte colony-stimulating factor \[G-CSF\] is allowed, and G-CSF is not allowed within 7 days before laboratory examination during the screening period);Platelet count ≥ 50×109/L (platelet transfusion is not allowed within 7 days before laboratory tests during the screening period).

Hemoglobin (HGB) ≥ 75 g/L (prior red blood cell \[RBC\] transfusions or recombinant human erythropoietin are allowed; Within 7 days before the laboratory examination during the screening period, red blood cell transfusion is not allowed).

(2) Other patients: Absolute neutrophil count (ANC) ≥ 1.5×109/L, Platelet count ≥ 100×109/L, Hemoglobin (HGB) ≥ 90 g/L Liver: total bilirubin (TBIL) ≤ 1.5×ULN, except for subjects with congenital bilirubinemia, such as Gilbert's syndrome (direct bilirubin ≤ 1.5×ULN); Glutamate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 3.0×ULN.

In the presence of liver metastases, both AST and ALT ≤ 5× ULN Kidney: creatinine clearance (Ccr) ≥ 30mL/min in patients with multiple myeloma, Creatinine ≤ 1.5×ULN in other patients.

Coagulation:

International Normalized Ratio (INR) ≤ 1.5, Activated partial thromboplastin time (APTT) or prothrombin time (PT) ≤ 1.5× ULN.

corrected serum calcium ≤ 14 mg/dL (≤ 3.5 mmol/L). left ventricular ejection fraction (LVEF) ≥ 50%. 11. The patient and his/her spouse agree to take effective contraceptive measures (excluding contraception during the safe period) from the time of signing the informed consent form to 6 months after the last dose.

Критерии исключения

• Within 14 days before the first dose: received plasmapheresis; Treatment with > 10 mg of prednisone or equivalent doses of systemic corticosteroids per day for more than 3 consecutive days (short-term use for the prevention of contrast allergy can be enrolled).
• Patients have received systemic anti-myeloma therapy or investigational drug therapy within 28 days or 5 half-lives (whichever is shorter) prior to the first dose; Radiotherapy within 14 days prior to the first dose.
• Patients have received monoclonal antibody therapy within 30 days before the first dose.
• Patients have received autologous hematopoietic stem cell transplantation within 100 days before the first dose.
• Patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) or have a history of solid organ transplantation.
• Patients have received the same targeted therapy in the past (limited to phase Ia clinical trials).
• Patient has symptomatic brain metastases or meningeal metastases.
• The patient had symptomatic amyloidosis, active plasma cell leukemia, and active POEMS syndrome at the time of screening.
• There is evidence of cardiovascular risk, including any of the following: a. QTcF interval ≥ 470 ms (QT interval must be corrected by Fridericia formula \[QTcF\]). b. Evidence of currently clinically significant, untreated arrhythmias, including clinically significant electrocardiogram abnormalities such as degree 2 (Mobitz type II) or degree 3 atrioventricular conduction (AV) block. c. History of myocardial infarction, acute coronary syndrome (including unstable angina pectoris), coronary angioplasty, or stenting or bypass grafting within 6 months prior to screening. d. Grade III or IV heart failure(New York Heart Association Functional Grading System). e. Uncontrolled severe hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥ 100 mmHg).
• The patient has difficulty breathing or currently requires continuous oxygen therapy, or currently has active pneumonia or interstitial lung disease (except for mild cases as determined by the investigator).
• The patient has a history of other primary malignancies, except the following: cured malignancies with a very low risk of recurrence within 5 years, such as skin basal cell carcinoma and skin squamous cell carcinoma, carcinoma in situ of the cervix or breast.
• Patients have severe unhealed wound ulcers or fractures, or have undergone major surgery within 28 days prior to dosing or are expected to undergo surgery during the clinical study.
• Previous history of allergy to any component or excipient of DXC006.
• Active hepatitis B (HBV-DNA greater than the central upper limit of normal or HBV-DNA testing greater than 1000 copies /mL); Hepatitis C infection (positive for hepatitis C antigen or positive for hepatitis C RNA PCR).
• Seropositive for human immunodeficiency virus (HIV); Active syphilis (patients with positive syphilis antibodies can be included); Possible active tuberculosis (chest imaging within 3 months prior to first dosing indicating active tuberculosis infection).
• Patients had active bleeding within 30 days prior to screening, or were at risk of massive gastrointestinal bleeding or hemoptysis as determined by researchers; Or have inherited bleeding tendencies or coagulation disorders, or bleeding symptoms that require other medical intervention.
• Severe arteriovenous thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism, occurred within 6 months before the first dose.
• Female patients with a positive serological pregnancy test or who are breastfeeding.
• Active infections requiring medical treatment (CTCAE≥2); Uncontrollable pleural fluid, ascites, pericardial effusion requiring repeated drainage;
• Received live attenuated vaccine within 28 days before the first dose.
• The patient has other conditions that the investigator or sponsor has determined may affect the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Anhui Cancer Hospital — Хэфэй
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Hunan Cancer Hospital — Чанша
• The First Affiliated Hospital of Nanchang University — Nanchang
• Zhejiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT06224855 · DXC006-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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