An Open-Label Study to Evaluate PF-07994525 in Participants With Advanced Cancers

Официальное название

AN OPEN-LABEL PHASE 1 STUDY TO EVALUATE PF-07994525 IN PARTICIPANTS WITH ADVANCED MALIGNANCIES

Обзор

This is an open-label, dose escalation and dose expansion study evaluating the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), and antitumor activity of PF-07994525 in participants with R/R MM. The study will consist of 2 parts: Part 1 (Dose Escalation) will consist of PF-07994525 dose escalation to assess the safety, tolerability, and preliminary antitumor activity in participants with R/R MM. In Part 2 (Dose expansion), PF-07994525 may be evaluated in additional participants with R/R MM to further assess safety, PK, PD, and preliminary anti-tumor activity.

Вмешательства

• Препарат PF-07994525
  Oral administration
• Препарат Midazolam
  Oral administration

Первичные конечные точки

• Type, incidence and severity of participants with adverse events (AEs) [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Type, incidence and severity of participants with laboratory abnormalities [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Number of participants with dose modifications [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) [Срок оценки: Baseline to end of DLT evaluation period]
• Part 1: Recommended Monotherapy Dose for Expansion (RDE) [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Part 2: Recommended Dose for future development [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]

Вторичные конечные точки (12)

• Objective response rate (ORR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator. [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Complete response rate (CRR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator. [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Time to response (TTR) per IMWG as determined by investigator [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Duration of response (DOR) per IMWG as determined by investigator [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Duration of complete response (DOCR) per IMWG as determined by investigator [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Progression-free survival (PFS) per IMWG as determined by investigator [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Overall survival (OS) [Срок оценки: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Single, Multiple Dose and food effect: Maximum Observed Concentration (Cmax) [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single, Multiple Dose and food effect: Time to Maximum concentration (Tmax) [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single, Multiple Dose and food effect: AUC from time zero to time of last measurable concentration (AUClast) [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single Dose and food effect: Terminal Elimination half-life (t1/2) as data permit [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single Dose and food effect: AUC versus time curve from time 0 extrapolated to infinity (AUCinf) as data permit [Срок оценки: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]

Критерии участия

Критерии включения

• Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at the time of informed consent.
• Prior diagnosis of MM as defined according to IMWG criteria (Rajkumar et al. 2014)

Measurable disease based on IMWG criteria as defined by at least 1 of the following:

• Serum M-protein >0.5 g/dL by serum protein electrophoresis (SPEP)
• Urinary M-protein excretion >200 mg/24 hours by urine protein electrophoresis (UPEP)
• Serum immunoglobulin Free Light Chain (FLC) ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65)

• Participants must be refractory to, or intolerant to, all established therapies known to provide clinical benefit in multiple myeloma that are an appropriate therapeutic option, in the judgement of the investigator. A minimum of 3 prior lines of therapy are required.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Критерии исключения

• Active plasma cell leukemia, Smoldering MM, Waldenströms macroglobulinemia, Amyloidosis, POEMS Syndrome.
• Autologous stem cell transplant within 12 weeks prior to enrollment or active Graft-versus-host disease (GVHD).
• Active or suspected cerebral/meningeal disease related to the underlying malignancy.
• Any active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), known HIV or AIDS related illness, unless deemed not clinically significant by the investigator (eg, onychomycosis).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center — Coral Gables
• Sylvester Comprehensive Cancer Center - Coral Springs — Coral Springs
• University of Miami Hospital and Clinics - Deerfield Beach — Deerfield Beach
• University of Miami Hospital and Clinics - Doral — Doral
• Sylvester Comprehensive Cancer Center - Hollywood — Hollywood
• Sylvester Comprehensive Cancer Center — Miami
• University of Miami Hospital and Clinics — Miami
• Sylvester Comprehensive Cancer Center- Kendall — Miami
• … и ещё 9 центров

Канада · 1 центр

• Arthur J.E. Child Comprehensive Cancer Centre — Calgary

Идентификаторы

NCT: NCT07426757 · C6331001 · KAT2i

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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