A Study of QLC5508 Combinations in Patients With Advanced Solid Tumors

Официальное название

A Phase Ib/II, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administration of QLC5508 in Combination With Other Anti-tumor Agents in Patients With Advanced Solid Tumors

Обзор

QLC5508 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents in patients with advanced solid tumor patients.

Подробное описание

This is a phase Ib/II, open-label, multi-center, dose-escalation and expansion in Chinese subjects with advanced solid tumors. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents.

The target population of dose escalation part is patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.

Вмешательства

• Препарат QLC5508
  2.4 mg/kg and 2.0 mg/kg, Q3W/Q2W,administered as an IV infusion
• Препарат QL1706
  5 mg/kg ,Q3W,administered as an IV infusion
• Препарат Cisplatin/ Carboplatin
  Cisplatin(75 mg/m2; Q3W) / Carboplatin（AUC 5 mg/mL/min; Q3W）,administered as an IV infusion
• Препарат QL2107
  200 mg, Q3W,administered as an IV infusion
• Препарат Paclitaxel
  175 mg/m2, Q3W,administered as an IV infusion
• Препарат 5-fluorouracil (5-FU)
  800 mg/m2,Q3W(arm:QLC5508, QL2107 and 5-FU),administered as an IV infusion;1200 mg/m2, Q2W(arm:QLC5508, Oxaliplatin, 5-FU,and leucovorin),administered as an IV infusion
• Препарат Oxaliplatin
  30 mg/m2, Q2W,administered as an IV infusion

Первичные конечные точки

• Maximum tolerated dose (MTD) for combination-treatments (Phase Ib) [Срок оценки: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose]
• Recommended Phase II Dose (RP2D) for combination-treatments (Phase Ib) [Срок оценки: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose]
• Objective response rate (ORR) determined by investigators (Phase II) [Срок оценки: Approximately 12 months]

Вторичные конечные точки (12)

• ORR determined by investigators (Phase Ib) [Срок оценки: Approximately 12 months]
• Disease control rate (DCR) determined by investigators (Phase Ib and II) [Срок оценки: Approximately 12 months]
• Duration of response (DOR) determined by investigators (Phase Ib and II) [Срок оценки: Approximately 12 months]
• Progression-free survival (PFS) determined by investigators (Phase Ib and II) [Срок оценки: Approximately 12 months]
• Overall survival (OS) (Phase Ib and II) [Срок оценки: Approximately 24 months]
• Incidence and severity of adverse events (AEs) (Phase II) [Срок оценки: From the first dose through 90 days post end of treatment]
• Observed maximum plasma concentration (Cmax) of QLC5508 in advanced solid tumor (Phase Ib and II) [Срок оценки: From pre-dose to study completion, approximately 24 months]
• Time to reach maximum plasma concentration (Tmax) of QLC5508 (Phase Ib) [Срок оценки: From pre-dose to study completion, approximately 24 months]
• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of QLC5508 (Phase Ib) [Срок оценки: From pre-dose to study completion, approximately 24 months]]
• Observed maximum plasma concentration (Cmax) of QL1706 in advanced solid tumor (Phase Ib and II) [Срок оценки: From pre-dose to study completion, approximately 24 months]
• Observed maximum plasma concentration (Cmax) of QL2107 in advanced solid tumor (Phase Ib and II) [Срок оценки: From pre-dose to study completion, approximately 24 months]
• Percentage of participants with antibodies to QLC5508 in serum (Phase Ib and II) [Срок оценки: From pre-dose to study completion, approximately 24 months]

Критерии участия

Критерии включения

• At least 18 years of age at screening;
• Histologically or cytologically confirmed advanced solid tumors:

Dose escalation part will enroll participants who have progressed on or are intolerant to available standard therapies.

Dose expansion part will enroll participants who have not received prior treatment for advanced/metastatic diseases.

• At least one measurable target lesion according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1
• Life expectancy ≥12 weeks
• Female or male participants should be willing to use appropriate contraceptive measures throughout the study;
• Female participants should have a negative blood pregnancy test within 7 days prior to the first dose or have evidence of non-childbearing potential;
• A signed written Informed Consent Form

Критерии исключения

• . Received or undergoing any of the following treatment:

• Previous or current treatment with B7-H3 targeted therapy
• Previous or current treatment with topoisomerase I inhibitors
• Previous treatment with cytotoxic chemotherapy, investigational agents, traditional Chinese medicine with an anti-tumor indication and antitumor drugs within 14 days prior to the first dose
• Previous treatment with macromolecular antitumor drugs within 28 days prior to the first dose

f. Radiotherapy with a limited field of radiation within 2 weeks prior to the first dose; or more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first dose e. Pleural effusion or ascites requiring clinical intervention; or presence of pericardial effusion f. Major surgery within 4 weeks prior to the first dose g. Brain metastases; leptomeningeal or brainstem metastases; or spinal cord compression

• Unresolved AEs ≥ Grade 2 (CTCAE v5.0) from prior therapy except for alopecia and residual neuropathy
• Previous or concurrent primary malignancies
• Inadequate bone marrow reserve or organ dysfunction
• Evidence of cardiovascular risk
• Evidence of current severe or uncontrolled systemic diseases
• Severe infection within 4 weeks prior to the first dose; or uncontrolled active infection at screening
• Known or suspected interstitial lung disease; or other moderate to severe pulmonary diseases that significantly impair respiratory function and may interfere with the detection or management of drug-related pulmonary toxicity
• High risk of gastrointestinal or abdominal bleeding 10. Gastrointestinal diseases of clinical significance within 3 months prior to the first dose
• History of severe neuropathy or mental disorders
• History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to QLC5508 or any of the components of QLC5508
• Unlikely to comply with study procedures and requirements in the opinion of the investigator
• Any disease or condition that, in the opinion of the investigator, would compromise participant safety or interfere with study assessments

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 · 1 центр

• Shanghai East Hospital — Шанхай

Идентификаторы

NCT: NCT07256782 · QLC5508-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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