临床试验/NCT05919264

NCT05919264招募中1 期

A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors

Parabilis Medicines, Inc.46 个研究点分布在 2 个国家目标入组 619 人开始时间: 2023年5月23日最近更新: 2026年8月17日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Parabilis Medicines, Inc.
入组人数: 619
试验地点: 46
主要终点: During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic solid tumors or in participants with familial adenomatous polyposis (FAP).

详细描述

This is a FIH, Phase 1/2, multicenter, open-label, non-randomized, dose escalation, dose expansion, and multiple subcutaneous dose study to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of FOG-001 as monotherapy and in combination with other anticancer agents in participants with advanced or metastatic solid tumors likely or known to have a Wnt pathway activating mutation (WPAM), and FAP, a disorder of this pathway characterized by a germline mutation in the APC gene.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Adequate organ and marrow function.
•Additional Inclusion Criteria for Dose Escalation Cohorts (Part 1a and Part 1g):
•Diagnosis of treatment-refractory advanced/metastatic solid tumor that is non-MSI-H or non-dMMR colorectal cancer (CRC) or any other solid tumor with documented WNT- pathway activating mutations (WPAMs).
•Additional Inclusion Criteria for Dose Escalation Cohorts (Part 1b):
•Diagnosis of treatment-refractory advanced/metastatic non-MSI-H or non-dMMR CRC.
•At least one lesion that is suitable for a core needle biopsy.
•Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1c and Part 2c):
•Histologically, cytologically, or radiographically confirmed HCC with a documented WPAM (by local ctDNA or tumor NGS testing) in APC or CTNNB1
•Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1d, Part 1h, and Part 2d):
•Desmoid tumor (aggressive fibromatosis)
•Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-1 and Part 2f-1) FOG-001 + FOLFOX + Bevacizumab:
•Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR CRC
•Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible.
•One dose of mFOLFOX6 with or without bevacizumab in the unresectable or metastatic setting prior to enrollment is allowed.
•Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-2 and Part 2f-2): FOG-001 + Nivolumab
•Non-MSI-H or non-dMMR (by local testing) CRC with or without liver metastases.
•MSI-H CRC or solid tumors that are WPAM and resistant to a-PD-1/PD-L1
•Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible
•Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-3 and Part 2f-3): FOG-001 + Trifluridine/Tipiracil + Bevacizumab
•Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR (by local testing) CRC
•Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible.
•Monotherapy Dose Optimization (Part 1i): FAP
•Diagnosis of phenotypic classical FAP with a documented APC mutation
•Post-colectomy >6 months prior to first dose of study drug administration with measurable duodenal polyp burden
•Additional Inclusion Criteria for Dose Expansion Cohort (Part 2a):
•Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR (by local testing) CRC
•Additional Inclusion Criteria for Dose Expansion Cohort (Part 2b):
•Diagnosis of advanced or metastatic solid tumors with a documented WPAM (by local testing) or equivalent evidence

排除标准

•Known history of bone metastasis. Bone metastasis are allowed for patients with mCRPC. For participants with FAP, osteomas are allowed.
•Evidence of vertebral compression fracture or non-traumatic bone fracture within the past 12 months and who are not receiving antiresorptive therapy.
•Osteoporosis, which is defined as a T-score of ≤-2.5 at the lumbar spine (L1 - L4), left (or right) femoral neck or left (or right) total hip as determined by DXA scan.
•Uncontrolled inflammatory bowel disease (i.e., ulcerative colitis or Crohn's disease)
•Unstable/inadequate cardiac function.
•Has known meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases.
•Pregnant, lactating, or planning to become pregnant.
•Complete colectomy within 6 months of the first dose of study drug administration.

研究组 & 干预措施

Part 1a

Experimental

Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status

干预措施: FOG-001 (Drug)

Part 1b

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 2f-2

Experimental

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 1f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: mFOLFOX-6 (Drug)

Part 2e

Experimental

Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required)

干预措施: FOG-001 (Drug)

Part 2f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: mFOLFOX-6 (Drug)

Part 2c

Experimental

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

干预措施: FOG-001 (Drug)

Part 2b

Experimental

Solid Tumors with documented WPAM

干预措施: FOG-001 (Drug)

Part 1f-2

Experimental

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 2f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 1f-2

Experimental

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

干预措施: Nivolumab (Drug)

Part 1f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 2a

Experimental

MSS CRC, irrespective of WPAM status

干预措施: FOG-001 (Drug)

Part 2f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 2d

Experimental

Desmoid Tumors

干预措施: FOG-001 (Drug)

Part 2f-2

Experimental

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

干预措施: Nivolumab (Drug)

Part 2f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Bevacizumab (Drug)

Part 2f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Trifluridine/tipiracil (Drug)

Part 2f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Bevacizumab (Drug)

Part 1f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Bevacizumab (Drug)

Part 1c

Experimental

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

干预措施: FOG-001 (Drug)

Part 1f-1

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 1f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Trifluridine/tipiracil (Drug)

Part 1g

Experimental

Solid Tumors with documented WPAM (known WPAM negative participants are not eligible)

干预措施: FOG-001 (Drug)

Part 1h

Experimental

Desmoid Tumors

干预措施: FOG-001 (Drug)

Part 1d-1

Experimental

Desmoid Tumors

干预措施: FOG-001 (Drug)

Part 1f-3

Experimental

MSS CRC (known WPAM negative participants are not eligible)

干预措施: Bevacizumab (Drug)

Part 1d-2

Experimental

Desmoid Tumors

干预措施: FOG-001 (Drug)

Part 1i

Experimental

Familial adenomatous polyposis (FAP)

干预措施: FOG-001 (Drug)

结局指标

主要结局

During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0

时间窗: Through study completion, an average of 10 months

Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0

During dose escalation characterize dose-limiting toxicities (DLTs)

时间窗: 1 treatment cycle (28 days)

Incidence of DLTs

During dose expansion describe the Overall Response Rate using RECIST v1.1

时间窗: Every 63 days until study completion, approximately 10 months on average

The rate of objective responses (Partial \& Complete) using RECIST v1.1

During dose expansion describe the Disease Control Rate using RECIST v1.1 (Part 2a only)

时间窗: 4 months

The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1

During dose expansion describe the PSA30 response rate for participants with prostate cancer

时间窗: Baseline, weekly during the first 2 cycles (56 days), bi-weekly during the Cycle 3 (28 days), and then monthly (up to approximately 7 months)

The response to treatment as a 30% or greater reduction in PSA levels from baseline

次要结局

During dose escalation and expansion describe the Disease Control Rate using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion describe the Time To Progression using RECIST v1.1(From date of randomization until the date of first disease progression, an average of 10 months)
During dose escalation and expansion describe radiographic Progression Free Survival for participants with prostate cancer(From date of randomization until the date of first disease progression, an average of 10 months)
Maximum observed plasma concentration (Cmax) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma(During first 2 cycles (56 days))
Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Clearance (CL) of FOG-001 from the plasma(During first 2 cycles (56 days))
Volume of distribution of FOG-001(During first 2 cycles (56 days))
During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors(During first 2 cycles (56 days))
During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion to describe Duration of Response using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion describe Progression Free Survival(From date of randomization until the date of first disease progression, an average of 10 months)
Maximum observed plasma concentration (Cmax) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma(During first 2 cycles (56 days))
Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites(During first 2 cycles (56 days))
Clearance (CL) of FOG-001 from the plasma(During first 2 cycles (56 days))
Volume of distribution of FOG-001(During first 2 cycles (56 days))
During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug(Through Part 1 study completion)
Rate of DLTs across dose levels(During Cycle 1 (28 days))
During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors(During first 2 cycles (56 days))
During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion to describe Duration of Response using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion describe Progression Free Survival(From date of randomization until the date of first disease progression, an average of 10 months)
During dose escalation and expansion describe the Disease Control Rate using RECIST v1.1(Every 63 days until study completion, approximately 10 months on average)
During dose escalation and expansion describe the Time To Progression using RECIST v1.1(From date of randomization until the date of first disease progression, an average of 10 months)
During dose escalation and expansion describe radiographic Progression Free Survival for participants with prostate cancer(From date of randomization until the date of first disease progression, an average of 10 months)

研究者

发起方

Parabilis Medicines, Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (46)

Loading locations...

相似试验

招募中

1 期

Study of GS-0201 Alone and in Combination in Participants With Advanced Solid TumorsAdvanced Solid Tumors

NCT06167317Gilead Sciences278

终止

2 期

Tarceva Surgery for Resectable Stage IIIA(N2) and IIIB (T4 N2) Non-Small-Cell Lung CancerLung Cancer

NCT00063258M.D. Anderson Cancer Center5

招募中

1 期

A Study to Investigate FP002 in Subjects With Advanced MalignanciesAdvanced Solid Tumor

NCT05982080Guangdong Fapon Biopharma Inc.27

已完成

2 期

Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive DiseasePeripheral Arterial Disease

NCT00368797Sanofi125

终止

2 期

Safety and Efficacy Study of Glufosfamide in Patients With Recurrent Sensitive Small Cell Lung CarcinomaCarcinoma, Small Cell Lung

NCT00435578Threshold Pharmaceuticals50