A Phase I Study to Investigate the Safety and Tolerability of KGX101 Monotherapy and Combination Therapy With Envafolimab in Advanced or Metastatic Solid Tumor Patients

Официальное название

A Phase I , Open Label, Multi-center Study to Assess the Safety and Tolerability of KGX101 Mono and Combo Therapy With Envafolimab in Advanced or Metastatic Solid Tumor Patients

Обзор

This is a phase I, open-label, multi-center, dose escalation and expansion study in advanced or metastatic solid tumor patients. The're are two goals set in this study: one is to explore the safety and tolerability of KGX101 when mono and combo with envafolimab in Chinese patients, the other is to determine recommended phase 2 dose of KGX101 mono and combo with envafolimab. Participants will: 1. Take drug KGX101 mono or combo with envafolimab every 3 weeks; 2. Visit the clinic for checkups and tests. Schedule will be about 6-8 times in the first month and then about every 3 weeks afterwards.

Вмешательства

• Препарат KGX101 injection
  KGX101 is a heterodimeric IL-12 prodrug with the C-terminus of IL-12 fused with ADCC-impaired IgG1 Fc and the N-terminus of IL-12 masked using the IL-12 binding domains of IL-12Rβ1 and IL-12Rβ2. KGX101 injection is a sterile, white or white-like lyophilized powder, supplied at 4.0 mg/vial for single use.
• Препарат Envafolimab
  Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.

Первичные конечные точки

• Numbers of participants with adverse events [Срок оценки: From baseline to 30 days after the last dose administration.]
• Number of participants with dose limiting toxicities/DLT within DLT observation period [Срок оценки: From Day1 after the first priming dose of KGX101 until 21 days post the first target dose ofKGX101]
• Number of participants with changes of clinical lab abnormalities [Срок оценки: From screening until 90 days post the last dose administration]
• The maximum tolerated dose of KGX101 monotherapy and combination therapy with Envafolimab [Срок оценки: From Day 1 post the first dosing until 21 days post the the first target dosing]

Вторичные конечные точки (11)

• PK parameters: Maximum Concentration (Cmax) of total IL-12 [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters: Time of maximum observed concentration (Tmax)of total IL-12 [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters: Area under the curve (AUC) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters: Half- life (T1 /2) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters- Trough concentration (Ctrough) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters- Systemic clearance (CL) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• PK Parameters- Volume of distribution (Vd) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.]
• Immunogenicity- Anti-drug antibody (ADA) [Срок оценки: Part A: From pre-dose of the first dose of KGX101 treatment until 90 days afrer the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until 90 days after the last dose.]
• Number of participants with changes in the Overall Response (ORR) [Срок оценки: From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post the last treatment.]
• Progression free survival (PFS) per RECIST 1.1 [Срок оценки: From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.]
• Overall survival [Срок оценки: From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.]

Критерии участия

Критерии включения

• Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard of care, no further standard can be used, or standard of care is not fit;
• Eastern cooperative oncology grous performance status of 0-1;
• Has at least 1 measurable lesion per RECIST 1.1;
• Has adequate organ and bone marrow function as per study which including hemoglobin > 90 g/L, platelet count >=100\*10e9/L, absolute meutrophil count >=1.5\*10e9/L;
• Life expectancy of at least 3 months;
• Provision of signed and dated written inform consent prior to any study-related procedures, sampling and analyses.

Критерии исключения

• Active known second malignancy except adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, breast cancer;
• Patients with primary CNS malignancies;
• Evidence of severe or uncontrolled systemic diseases, including: active infection, hypertension, chronically unhealed wound or ulcers;
• Active autoimmnue disease requiring systemic treatment in the last 2 years, or immunodefiency which is on immunosuppressive therapy, chronic systemic or enteric steroid therapy;
• History of pneumonitis, interstitial lung disease which require steroids or has current pneumonitis/ interstitial lung disease;
• Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Beijing Cancer Hospital — Пекин
• Fudan university Shanghai Cancer Center — Шанхай
• Shanghai Chest Hospital — Шанхай

Идентификаторы

NCT: NCT07260305 · KGX101ST102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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