First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Официальное название

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Обзор

Study STX-478-101 (LY4064809) is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 (LY4064809) in participants with advanced solid tumors with P13Ka mutations. Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors. Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with hormone receptor positive (HR+) breast cancer. Part 3 will evaluate STX-478 as combination therapy with endocrine therapy (aromatase inhibitors, fulvestrant, tamoxifen, or imlunestrant) and a CDK4/6 Inhibitor (either Ribociclib, Palbociclib or Abemaciclib) in participants with HR+ breast cancer. Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Вмешательства

• Препарат STX-478
  STX-478 is a mutant-selective PI3Kα inhibitor
• Препарат Fulvestrant
  Fulvestrant
• Препарат Ribociclib
  Ribociclib
• Препарат Palbociclib
  Palbociclib
• Препарат Letrozole
  Letrozole
• Препарат Anastrozole
  Anastrozole
• Препарат Exemestane
  Exemestane
• Препарат Tamoxifen
  Tamoxifen
• Препарат Abemaciclib
  Abemaciclib
• Препарат Imlunestrant
  Imlunestrant

Первичные конечные точки

• Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [Срок оценки: First 28 days of treatment]
• Proportion of participants who experience at least 1 DLT during the first 28 days of treatment [Срок оценки: First 28 days of treatment]
• Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1 [Срок оценки: 12 months]
• Incidence of TEAEs/SAEs ≥ grade 2 [Срок оценки: 12 months]
• Frequency of TEAEs according to CTCAE v5.0 criteria [Срок оценки: 12 months]

Вторичные конечные точки (10)

• Cmax of STX-478 [Срок оценки: 12 months]
• AUC(0-inf) of STX-478 [Срок оценки: 12 months]
• AUC(0-t) of STX-478 [Срок оценки: 12 months]
• AUC(0-τ) of STX-478 [Срок оценки: 12 months]
• Change from baseline in ctDNA levels [Срок оценки: 12 months]
• Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c) [Срок оценки: 12 months]
• Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose [Срок оценки: 12 months]
• Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide [Срок оценки: 12 months]
• Change in ECOG performance status [Срок оценки: 12 months]
• Disease Control Rate (DCR) per RECIST v1.1, measured as percentage of participants with Complete Response [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
• Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
• Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
• Is ≥18 years of age at the time of signing the ICF
• Has an ECOG performance status score of 0 or 1 at screening
• Has adequate organ function as defined per protocol

Критерии исключения

• Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
• Has symptomatic brain or spinal metastases
• Has an established diagnosis of uncontrolled diabetes mellitus (defined as HbA1c ≥8% and/or FBG ≥140 mg/dL \[7.7 mmol/L\] and/or requiring or required insulin).
• Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
• Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
• Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.
• Has had radiotherapy within 14 days before the initiation of study treatment

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 · 28 центров

• Ellison Clinic at Saint John's — Los Angeles
• UCSF Medical Center at Mission Bay — San Francisco
• University of Colorado Cancer Center — Aurora
• Yale-New Haven Hospital — New Haven
• Florida Cancer Specialists ORLANDO/DDU — Lake Mary
• Moffitt Cancer Center — Tampa
• Winship Cancer Institute, Emory University — Atlanta
• University of Iowa — Iowa City
• … и ещё 20 центров

Испания · 12 центров

• Hospital Quiron Barcelona — Barcelona
• South Texas Accelerated Research Therapeutics (START) Barcelona- HM Nou Delfos — Barcelona
• Instituto Oncologico Dr Rosell (IOR) — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital San Pedro — Logroño
• MD Anderson Cancer Center — Madrid
• Hospital Clinico San Carlos — Madrid
• Hospital Universitario Fundación Jiménez Díaz — Madrid
• … и ещё 4 центра

Италия · 9 центров

• Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo — Alessandria
• Spedali Civili di Brescia — Brescia
• Istituto Nazionale per lo Studio e la Cura dei Tumori — Milan
• Istituto Europeo di Oncologia — Milan
• Fondazione IRCCS San Gerardo dei Tintori — Monza
• Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara — Pisa
• Ospedale Santa Maria delle Croci — Ravenna
• Fondazione Policlinico Universitario Agostino Gemelli — Roma
• … и ещё 1 центр

Франция · 6 центров

• Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest — Bordeaux
• Centre Leon Berard — Lyon
• Institut Paoli-Calmettes — Marseille
• Centre Antoine-Lacassagne — Nice
• Institut Claudius Regaud — Toulouse
• Gustave Roussy — Villejuif

Япония · 4 центра

• National Hospital Organization Kyushu Cancer Center — Fukuoka
• Kansai Medical University Hospital — Hirakata
• The Cancer Institute Hospital of JFCR — Kōtō City
• Kyoto University Hospital — Kyoto

Бельгия · 2 центра

• Institut Jules Bordet — Anderlecht
• UZ Leuven — Leuven

Нидерланды · 2 центра

• Netherlands Cancer Institute — Amsterdam
• Erasmus MC — Rotterdam

Германия · 1 центр

• Universitätsklinikum Erlangen — Erlangen

Ирландия · 1 центр

• Mater Misericordiae Hospital — Dublin

Идентификаторы

NCT: NCT05768139 · 27691 · 2023-504807-94-00 · 2023-000442-41 · J6M-OX-JSGA · STX-478-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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