First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations

Обзор

Study STX-721-101/PFL-721CI101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721/PFL-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR or HER2 exon 20 insertion (ex20ins) mutations.

Вмешательства

• Препарат STX-721/PFL-721 (Escalated)
  STX-721/PFL-721 dose will be escalated per cBLRM-design.
• Препарат STX-721/PFL-721 (3 dose levels)
  Participants will receive STX-721/PFL-721 at one of three dose levels.
• Препарат STX-721/PFL-721 (RP2D)
  Participants will receive the RP2D of STX-721/PFL-721.

Первичные конечные точки

• Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment [Срок оценки: 28 days]
• Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment [Срок оценки: 28 days]
• Part 2 RP2D Selection: C(max) of STX-721/PFL-721 [Срок оценки: 1 year]
• Part 2 RP2D Selection: AUC(0-inf) of STX-721/PFL-721 [Срок оценки: 1 year]
• Part 2 RP2D Selection: AUC(0-t) of STX-721/PFL-721 [Срок оценки: 1 year]
• Part 2 RP2D Selection: AUC(0-τ) of STX-721/PFL-721 [Срок оценки: 1 year]
• Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment. [Срок оценки: 1 year]
• Part 3 Dose Expansion: Number of participants with confirmed ORR defined as the percentage of participants with PR or CR based on RECIST v1.1 per investigator assessment. [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation
• Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR/HER2 exon 20 insertion mutations confirmed by qualified local laboratories
• Part 1: Has received all approved therapies for advanced or metastatic NSCLC or is ineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, prior lines of approved treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicated
• Has documented tumor progression (based on radiological imaging)
• Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profiling
• Has at least one measurable tumor lesion per RECIST v1.1
• Is ≥18 years of age at the time of signing the ICF
• Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Критерии исключения

• Has a tumor that is known to harbor EGFR ex20ins p.H773\_V774insH variant, or any EGFR kinase domain activating mutation concurrent with either a T790M and/or C797S resistance mutations
• Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC
• Has symptomatic brain or spinal metastases
• Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy
• Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., could compromise the participant's well-being) or would prevent, limit, or confound the protocol-specified assessments

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• City of Hope — Duarte
• City of Hope — Huntington Beach
• City of Hope — Irvine
• Levine Cancer Institute - Charlotte — Charlotte
• Thomas Jefferson University Research Facility — Philadelphia
• SCRI Oncology Partners - PPDS — Nashville
• University of Texas MD Anderson Cancer Center — Houston
• University of Utah - Huntsman Cancer Institute - PPDS — Salt Lake City
• … и ещё 1 центр

Испания · 4 центра

• Hospital Regional Universitario de Malaga - Hospital General — Málaga
• Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario Virgen del Rocio — Seville

Франция · 3 центра

• EDOG Institut de Cancerologie de l'Ouest - PPDS — Saint-Herblain
• Institut Claudius Regaud - PPDS — Toulouse
• Gustave Roussy — Villejuif

South Korea · 3 центра

• Chungbuk National University Hospital — Cheongju-si
• CHA Bundang Medical Center, CHA University — Seongnam-si
• Seoul National University Hospital — Seoul

Германия · 2 центра

• Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30 — Berlin
• Universitätsklinikum Carl Gustav Carus an der TU Dresden — Dresden

Тайвань · 2 центра

• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Нидерланды · 1 центр

• Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis — Amsterdam

Идентификаторы

NCT: NCT06043817 · STX-721-101/PFL-721CI101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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