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临床试验/2023-509220-17-00
2023-509220-17-00招募中2 期

A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the DNA Polymerase Theta Inhibitor ART6043 Administered Orally as Monotherapy and in Combination to Patients with Advanced or Metastatic Solid Tumors

Artios Pharma Limited20 个研究点 分布在 1 个国家目标入组 55 人开始时间: 2024年7月19日最近更新:
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试验速览

阶段
2 期
状态
招募中
发起方
入组人数
55
试验地点
20
主要终点
Part A: Incidence of Dose Limiting Toxicities (DLTs); incidence and severity of Adverse Events (CTCAE v5.0)
研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Part A: To assess the safety and tolerability of ART6043 given orally in patients with advanced or metastatic solid tumors and to determine the MTD and/or RP2D(s) of ART6043 as monotherapy, in combination with olaparib and in combination with niraparib

Part B1: To further assess the safety and tolerability of ART6043 given orally in combination with PARPi at the RP2D(s).

Part B2: To assess preliminary signs of efficacy with ART6043 in combination with PARPi compared to PARPi alone in patients with HER2-ve locally advanced or metastatic breast cancer with a g/sBRCA mutation.

入排标准

年龄范围
18 years 至 65+ years（65+ Years, 18-64 Years）
接受健康志愿者
否

入选标准

  • •Have discontinued all previous chemotherapeutic agents, non-hormonal targeted therapy, or investigational drugs for at least 21 days or 5 half-lives (not including palliative radiotherapy at focal sites), whichever is shorter. Endocrine and hormonal therapies for the treatment of cancer must have been discontinued (unless for the treatment of Prostate Cancer) at least 7 days before receiving study medication. Palliative radiotherapy must have completed prior to start of study treatment
  • •Specific to Part A2/A3: Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes based on available, pre-existing testing
  • •Specific to Part A2/A3: Patients for whom a PARPi is an appropriate treatment option. Patients may have received prior treatment with a PARPi.
  • •Specific to Part B: Histologically or cytologically confirmed HER2-ve locally advanced or metastatic carcinoma of the breast.
  • •Specific to Part B: Documentation of a deleterious or suspected deleterious g/sBRCA mutation and/or PALB2 mutation.
  • •Specific to Part B: Patients must have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.
  • •Specific to Part B: Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated.
  • •Specific to Part B: Patients must have received no or ≤1 month of prior treatment with a PARPi.
  • •Resolution of all toxicities of prior therapy or surgical procedures.
  • •Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • •Have adequate organ function
  • •Patients of childbearing potential and patients with partners of childbearing potential must be willing to follow contraceptive requirements during their participation in the study and for the appropriate period after the last dose of study drug
  • •Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.
  • •Specific to Part A1: Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes
  • •Specific to Part A1 for Spain only: Patient that is not eligible for curative treatment, for whom standard of care therapies have failed.
  • •Specific to Part A1/A2/A3: At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation (prostate cancer patients only).

排除标准

  • •Patients who are pregnant (lack of pregnancy confirmed by a urine or serum pregnancy test within 5 days prior to receiving first dose of study treatment in patients of childbearing potential) or breast feeding.
  • •Known hypersensitivity/history of allergy to any of the components of ART6043, olaparib or niraparib (as applicable).
  • •Specific to Part B: First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy.
  • •Specific to Part B: Inflammatory breast cancer.
  • •Have a serious concomitant systemic disorder that would compromise the patient's ability to adhere to the protocol.
  • •Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
  • •Have ongoing interstitial lung disease or pneumonitis.
  • •Have any major gastrointestinal issues that could impact absorption of ART6043, Niraparib or Olaparib.
  • •Patients with brain metastases (patients with treated brain metastases could be eligible if follow-up brain imaging after central nervous system-directed therapy shows no evidence of progression).
  • •Have received a live vaccine within 30 days before the first dose of study treatment.
  • •Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access), or minor surgery within 1 week of entry into the study.
  • •Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.

结局指标

主要结局

Part A: Incidence of Dose Limiting Toxicities (DLTs); incidence and severity of Adverse Events (CTCAE v5.0)

Part A: Incidence of Dose Limiting Toxicities (DLTs); incidence and severity of Adverse Events (CTCAE v5.0)

Part B1: Incidence and severity of adverse events (CTCAE v5.0)

Part B1: Incidence and severity of adverse events (CTCAE v5.0)

Part B2: Progression free survival (PFS) (based on RECIST v1.1)

Part B2: Progression free survival (PFS) (based on RECIST v1.1)

次要结局

  • Part B2: Incidence and severity of Adverse events (CTCAE v5.0)
  • Best overall response (BOR), Objective Response Rate (ORR), Disease control rate (DCR), Duration of response (DOR) and change in tumor size
  • Serological tumor markers
  • Part A and B1: Progression free survival (PFS)
  • Overall survival (OS)
  • ART6043 and ART7276 plasma concentration data
  • ART6043 Urine concentration data
  • Olaparib and niraparib plasma concentration data
  • Archival tumor or pre-dose tumor biopsy

研究者

发起方
Artios Pharma Limited
申办方类型
Pharmaceutical company
责任方
Principal Investigator
主要研究者

Chief Medical Officer

Scientific

Artios Pharma Limited

研究点 (20)

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