A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors

Официальное название

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-08032562 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS

Обзор

The purpose of this study is to learn about the safety and effects of the study medicine when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment to stop the growth of cancer. This study also aims to find the best amount of study medication. This study is seeking participants that have advanced or metastatic breast cancer (BC), or advanced or metastatic colorectal cancer (CRC). All participants in this study will take the study medication (PF-08032562) as pill by mouth. This will be repeated for 28-day cycles. Depending on which part of the study participants are enrolled into, they will receive the study medication PF-08032562 alone or in combination with other anti-cancer medications. The study medication (PF-08032562) will be taken by mouth (PO) in combination with other anti-cancer medications given in the study clinic by intramuscular (IM) injection into the muscle or intravenous (IV) infusion that is directly injected into the veins at different times (depending on the treatment) during the 28-day cycle. The study may also test different schedules.

Вмешательства

• Препарат PF-08032562
  Taken by mouth (PO)
• Препарат Fulvestrant
  Selective Estrogen Receptor Degrader (SERD)
• Препарат Cetuximab
  Monoclonal antibody (EGFR inhibitor)
• Препарат Fluorouracil
  Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
• Препарат Oxaliplatin
  Part of FOLFOX chemotherapy regimen platinum based compound (alkylating agent)
• Препарат Leucovorin
  Part of FOLFOX chemotherapy regimen (folic acid analog)
• Препарат Bevacizumab
  Monoclonal antibody (VEG-F inhibitor)

Первичные конечные точки

• Part 1 (Dose Escalation): Number of participants with Dose-Limiting Toxicities (DLT) [Срок оценки: Baseline up to 28 days]
• Part 1 (Dose Escalation): Number of participants with laboratory abnormalities [Срок оценки: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first]
• Part 1 (Dose Escalation): Incidence of Adverse Events (AEs) [Срок оценки: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first]
• Part 2 (Dose Expansion): Objective Response Rate (ORR) [Срок оценки: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)]

Вторичные конечные точки (12)

• Part 1 & Part 2: Maximum Observed Serum Concentration (Cmax) [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1 & Part 2: Time to Reach Maximum Observed Serum Concentration (Tmax) [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast) [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1: Effect of Food on Cmax [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1: Effect of Food on Tmax [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1: Effect of Food on AUClast [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 1: Percent change of immune cells within tumors based on immunohistochemistry assessment [Срок оценки: Baseline through end of Cycle 1 (each cycle is 28 days)]
• Part 2 (Dose Expansion): Number of participants with laboratory abnormalities [Срок оценки: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first]
• Part 2 (Dose Expansion): Incidence of Adverse Events (AEs) [Срок оценки: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first]
• Part 1 & Part 2: Objective Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [Срок оценки: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)]
• Part 1 & Part 2: Disease Control Rate (DCR) as per RECIST v1.1 [Срок оценки: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)]
• Part 1 & Part 2: Clinical Benefit Rate (CBR) as per RECIST v1.1 [Срок оценки: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)]

Критерии участия

Критерии включения

• 18 years of age or older
• Advanced or metastatic cancer of the breast or colon Part 1A: metastatic or advanced breast cancer or colorectal cancer for which no standard therapy is available Part 1B: metastatic or advanced breast cancer with disease progression after at least 1 line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting Part 1C: metastatic or advanced colorectal cancer with at least having received chemotherapy and/or targeted therapy if appropriate Part 1D: metastatic or advanced colorectal cancer without any prior chemotherapy for advanced or metastatic disease Part 2A: metastatic or advanced breast cancer with disease progression after at least 1 prior line of CDK4/6 inhibitor and at least 1 prior line of endocrine therapy Part 2B: metastatic or advanced colorectal cancer with at least having received chemotherapy and/or targeted therapy if appropriate Part 2C: metastatic or advanced colorectal cancer without any prior chemotherapy for advanced or metastatic disease
• Measurable disease
• ECOG performance status 0 or 1

Критерии исключения

• Active malignancy within 3 years prior to enrollment
• Known symptomatic brain metastases requiring steroids
• Advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term
• Prior irradiation to >25% of the bone marrow
• Hypertension that cannot be controlled by optimal medical therapy
• Renal impairment
• Hepatic dysfunction
• Cardiac abnormalities
• Active bleeding disorder
• Active or history of clinically significant GI disease
• Other unacceptable abnormalities as defined by protocol

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 · 13 центров

• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• START Midwest, LLC — Grand Rapids
• Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy — Long Island City
• Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street — New York
• Memorial Sloan Kettering Cancer Center 53rd street. — New York
• Memorial Sloan Kettering Cancer Center - Main Campus — New York
• The University of Texas MD Anderson Cancer Center - Conroe — Conroe
• The University of Texas - M.D. Anderson Cancer Center — Houston
• … и ещё 5 центров

Идентификаторы

NCT: NCT07318805 · C6321001 · 2025-524387-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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