A Phase I Clinical Study of HS-20117 in Participants With Advanced Solid Tumors

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-20117 in Participants With Advanced Solid Tumors

Обзор

HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HS-20117 as a monotherapy for participants with advanced solid tumors.

Подробное описание

This is a multicenter, open-label, Phase I clinical study of HS-20117 to evaluate the safety, tolerability, PK, immunogenicity and efficacy in participants with advanced solid tumors. The study consists of phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 in participants with locally advanced or metastatic NSCLC who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy with EGFR exon 20 insertion mutations, and to explore the efficacy of HS-20117 in participants with other advanced solid tumors.

Вмешательства

• Препарат HS-20117
  Phase Ia: patients will receive HS-20117 starting at 400 mg, and subsequent cohorts will test escalating doses, if tolerated, until a maximum tolerated dose (MTD) or maximum applicable dose (MAD) is defined. Phase Ib: patients will receive HS-20117 at MED or MAD

Первичные конечные точки

• [Phase 1a] Maximum tolerated dose (MTD) of HS-20117 [Срок оценки: Cycle 1 (28 days)]
• [Phase 1a] Maximum applicable dose (MAD) of HS-20117 [Срок оценки: Cycle 1 (28 days)]
• [Phase 1b] Efficacy of HS-20117: Objective response rate (ORR) [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]

Вторичные конечные точки (12)

• [phase 1a and 1b] 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 1a and 1b] 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 1a and 1b] 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.]
• [phase 1a and 1b] PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117 [Срок оценки: From the date of first dose until 30 days after the final dose. A cycle is 28 days]
• [phase 1a] PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117 [Срок оценки: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a] PK parameters: Terminal elimination half-life (t1/2) of HS-20117 [Срок оценки: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a] Efficacy of HS-20117: ORR [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: disease control rate (DCR) [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: duration of response (DoR) [Срок оценки: From the date of CR, PR until the date of disease progression or death, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: progression free survival (PFS) [Срок оценки: From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or death, approximately 2 years.]
• [phase 1b] Efficacy of HS-20117: overall survival (OS) [Срок оценки: From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years]
• [phase 1a and 1b] Immunogenicity of HS-20117 [Срок оценки: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).]

Критерии участия

Критерии включения

• Males or females aged 18 - 75 years (inclusive).
• For the phase Ia study: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR-activating mutations who have progressed after or are intolerant to or not available to standard of care (SoC).
• For the phase Ib study:

Cohort A: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR exon 20ins mutations who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy.

Cohort B: Participants with other advanced solid tumors who have progressed after prior SoC or are intolerant to SoC.

• 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:

• For the phase Ib study Cohort A: Previous or current treatment with EGFR exon 20ins targeted therapy.
• Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of HS-20117.
• Cytotoxic chemotherapies, investigational drugs or other systematic anti-tumor therapies within 3 weeks prior to the first dose of HS-20117.
• Antibodies within 4 weeks prior to the first dose of HS-20117.
• Local radiotherapy within 2 weeks prior to the first dose of HS-20117, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of HS-20117.
• Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
• Major surgery within 4 weeks prior to the first dose of HS-20117.
• 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 within 1 month prior to the first dose of HS-20117.
• Severe arteriovenous thrombosis occurred within 3 months prior to the first dose of HS-20117
• Serious infection within 4 weeks prior to the first dose of HS-20117.
• Active infectious diseases.
• Interstitial lung disease (ILD).
• Serious neurological or mental disorders.
• History of hypersensitivity to any component of HS-20117 or similar drugs.
• 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

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical University Cancer Institute and Hospital — Тяньцзинь

Идентификаторы

NCT: NCT05940116 · HS-20117-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗