A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

Официальное название

A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-5125 in Adults With Selected Advanced Solid Tumors

Обзор

This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-5125 for the treatment of selected locally advanced or metastatic solid tumors with particular focus on Colorectal carcinoma (CRC).

Вмешательства

• Препарат APL-5125
  APL-5125 is an oral drug (capsule) taken daily in 28-day cycles

Первичные конечные точки

• Incidence of Treatment Emergent Adverse Events [Safety] [Срок оценки: Through study completion, approximately one year]
• Incidence of dose limiting toxicities [Tolerability] (Phase 1) [Срок оценки: Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)]
• Determine Recommended Phase 2 Dose (RP2D) levels of APL-5125 in participants with selected advanced solid tumors (Phase 1) [Срок оценки: Approximately one year]
• Assess the anti-tumor activity of APL-5125 in patients with Colorectal carcinoma (Phase 2) [Срок оценки: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)]

Вторичные конечные точки (8)

• Assess the preliminary anti-tumor activity of APL-5125 in colorectal carcinoma patients (Phase 1) [Срок оценки: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)]
• Assess the pharmacokinetics (PK) of APL-5125 (Phase 1) [Срок оценки: On days 1, 2, 4, 8, 15 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).]
• Assess the pharmacokinetics (PK) of APL-5125 (Phase 1) [Срок оценки: On days 1, 2 ,4, 8, 15 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).]
• Evaluate biomarker(s) in the tumor [Срок оценки: Through study completion, approximately one year]
• Further assess the anti-tumor activity of APL-5125 (Phase 2) [Срок оценки: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)]
• Incidence of treatment emergent adverse events [Further Safety] (Phase 2) [Срок оценки: Through study completion (approximately 2 years)]
• Further assess the PK of APL-5125 (Phase 2) [Срок оценки: On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).]
• Further assess the PK of APL-5125 (Phase 2) [Срок оценки: On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).]

Критерии участия

Критерии включения

• 18 years or older
• Phase 1: Histologically confirmed locally advanced, inoperable, or metastatic tumor; Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma.
• For Phase 1 sub-studies: Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma, Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Endometrial Adenocarcinoma, Triple Negative Breast Cancer, Ovarian Cancer, Prostate Cancer
• Phase 2: Colorectal carcinoma
• No available standard of care therapy or participant is ineligible for standard of care therapy, except in CRC tumor type in which participant must have previously received all the following therapeutic agents:

• fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
• an anti-VEGF therapy
• if wt-RAS (wt-KRAS and wt-NRAS), an anti-EGFR therapy
• Eastern Cooperative Oncology Group (ECOG) ≤1
• Body Weight ≥40 kg.
• Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse
• Male participants must be willing to use specific contraception and not plan to impregnate a female partner or donate sperm while on study
• Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

Критерии исключения

• Certain medical conditions such as: active brain metastases, carcinomatous meningitis, unstable angina pectoris, myocardial infarction or clinically significant ventricular arrhythmias, symptomatic congestive heart failure, uncontrolled active infection, history of significant hemorrhage within 4 weeks of the first dose date, intestinal disease or major gastric surgery, arterial thrombosis within 6 months of screening
• Certain prior therapies such as: anti-cancer treatment within 2 weeks of Cycle 1 Day 1, prior radiotherapy within 14 days before screening, active anti-coagulation therapy, over the counter or prescription medications within 14 days or 5 half-lives prior to cycle 1 day 1, herbal medicines and supplements within 14 days
• Major surgery within 1 month of screening
• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count < 1.5 x 10\^9/L
• Platelet count < 100 x 10\^9/L
• Hepatic function:

• Aspartate aminotransferase and/or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) (>5 x ULN for subjects with liver metastases)
• Total bilirubin >1.5 × ULN (except participants with Gilbert's syndrome).
• Albumin < 3 g/dL
• Calculated or measured creatinine clearance of <60 mL/minute calculated using the formula of Cockcroft and Gault (\[140 - Age\] × Mass \[kg\] / \[72 × serum creatinine mg/dL\]). Multiply result by 0.85 if female.
• Fridericia's corrected QT interval (QTcF) >470 msec or a family history of Long QT Syndrome.
• Cardiac function: Echocardiogram (or MUGA) showing Left Ventricular Ejection Fraction (LVEF) <45% at rest
• Infectious diseases: positive for HIV (unless controlled with active retroviral therapy), hepatitis B and hepatitis C

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 Orange County Lennar Foundation Cancer Center — Irvine
• Florida Cancer Specialists & Research Institute — Sarasota
• University of Michigan — Ann Arbor
• Duke Cancer Institute — Durham
• Carolina BioOncology Institute — Huntersville
• Medical University of South Carolina — Charleston
• Mary Crowley Cancer Research — Dallas
• … и ещё 1 центр

Идентификаторы

NCT: NCT06399757 · AP10CP01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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