A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

Официальное название

A Phase Ib/III Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Immunogenicity of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

Обзор

HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of this study is to assess the safety, efficacy, pharmacokinetics and immunogenicity of HS-20117 combined with Aumolertinib in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions \[Exon 19del\] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

Подробное описание

This is a multicenter Phase Ib/III clinical study evaluating the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20117 in combination with aumolertinib in subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The study is divided into two phases, Phase Ib, a dose expansion study and Phase III, a confirmatory study. In the dose expansion phase (Phase Ib), HS-20117 will first be studied in combination with the standard dose of aumolertinib, to assess the efficacy, safety, tolerability, PK profile, and immunogenicity of HS-20117 in combination with aumolertinib in the target population, as well as to determine the recommended Phase III dose (RP3D). Following confirmation of the safety and efficacy of HS-20117 in combination with aumolertinib and RP3D in Phase Ib, a randomized, active-controlled, open-label, multicenter Phase III study will be initiated to assess the efficacy and safety of HS-20117 in combination with aumolertinib versus aumolertinib in the target population in the confirmatory study phase.

Вмешательства

• Препарат HS-20117
  Participants will receive HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)
• Препарат Aumolertinib
  110 mg orally once daily.

Первичные конечные точки

• [Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs) [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months]
• [Phase III] Progression-Free Survival (PFS) According to RECIST v1.1 by Independent Review Committee(IRC) [Срок оценки: Up to approximately 40 months]

Вторичные конечные точки (12)

• [Phase Ib and III] Overall Survival (OS) [Срок оценки: Approximately 60 months]
• [Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.]
• [Phase Ib and III] Duration of response (DoR) According to RECIST v1.1 by INVs [Срок оценки: From the date of CR, PR until the date of disease progression or death, approximately 40 months.]
• [Phase Ib and III] Progression-Free Survival (PFS) According to RECIST v1.1 by INVs [Срок оценки: Up to approximately 40 months]
• [Phase III] ORR According to RECIST v1.1 by INVs [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months]
• [Phase III] ORR According to RECIST v1.1 by IRC [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months]
• [Phase III] DCR According to RECIST v1.1 by IRC [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.]
• [Phase III] DoR According to RECIST v1.1 by IRC [Срок оценки: From the date of CR, PR until the date of disease progression or death, approximately 40 months.]
• [Phase Ib and III] Incidence and severity of treatment-emergent adverse events [Срок оценки: From the date of first dose until 90 days after the final dose. A cycle is 28 days.]
• [Phase Ib and III] Immunogenicity of HS-20117 [Срок оценки: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).]
• [Phase Ib] PK parameters: Maximum serum concentration (Cmax) of HS-20117 [Срок оценки: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [Phase Ib] PK parameters: Trough serum concentration (Ctrough) of HS-20117 [Срок оценки: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]

Критерии участия

Критерии включения

• Males or females aged 18 - 75 years (inclusive).
• Participants with newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic EGFR-sensitive mutated NSCLC (stage IIIB/IIIC/IV) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation.
• Agree to provide fresh or archival tumor tissue.
• At least one target lesion per the RECIST v1.1.
• ECOG performance status of 0-1.
• Minimum life expectancy > 12 weeks.
• Males or Females should be using adequate contraceptive measures throughout the study.
• Females must not be pregnant at screening or have evidence of non-childbearing potential.
• Have signed Informed Consent Form.

Критерии исключения

• Received or are receiving the following treatments:

• Previous or current treatment with MET targeted therapy or EGFR targeted antibodies or antibody-drug conjugates (ADC).
• Traditional Chinese medicine indicated for tumors, major surgery or other local therapy within washout period to the first dose of study drug.
• Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
• Other investigational non-anti-tumor drugs, strong CYP3A4 inhibitors, strong inducers, drugs that are sensitive substrates of BCRP or P-gp, or drugs that prolong the QT interval within the washout period.
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• History of other primary malignancies.
• Untreated, or active central nervous system metastases.
• Inadequate bone marrow reserve or organ functions.
• Severe, uncontrolled or active cardiovascular disorders.
• Severe or uncontrolled systemic diseases.
• Severe bleeding symptoms or bleeding tendencies.
• Severe arteriovenous thrombosis occurred.
• Serious or active infection.
• Active infectious diseases.
• Interstitial lung disease (ILD).
• Serious neurological or mental disorders.
• History of hypersensitivity to any component of HS-20117 and Aumolertinib or their similar drugs.
• Female subjects who are pregnant, lactating, or planning to become pregnant or breastfeed during the study period or within 6 months after the last dose of the study drug.
• Subjects with a history of severe allergic reactions or those who have experienced severe infusion reactions
• Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Tianjin Medical University Cancer Institute and Hospital — Тяньцзинь
• Zhejiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT06417008 · HS-20117-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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