Phase II Open-label Study of ARX788 (Anti-HER2 Antibody Drug Conjugate (ADC)) for Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer
概览
- 阶段
- 2 期
- 干预措施
- ARX788
- 疾病 / 适应症
- HER2 Low Breast Carcinoma
- 发起方
- Laura Huppert, MD, BA
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
- 状态
- 尚未招募
- 最后更新
- 昨天
概览
简要总结
This phase II trial tests how well ARX788 works in treating patients diagnosed with HER2-low, locally advanced unresectable or metastatic breast cancer. ARX788 is an antibody-drug conjugate (ADC) that is given by infusion (diluted and injected slowly into veins). Antibodies are proteins which are naturally produced by the body's immune system to help fight infections. ARX788 consists of antibodies that have been attached to a toxin that has the potential to kill cancer cells. ARX788 sticks to a protein called human epidermal growth factor receptor (HER2), which is found on some breast cancer cells. Giving ARX788 may be safe and effective in treating patients with HER2-low locally advanced unresectable metastatic breast cancer.
详细描述
PRIMARY OBJECTIVES: I. To evaluate the objective response rate (ORR) of participants with HER2-low locally advanced unresectable/metastatic breast cancer on ARX788 monotherapy. SECONDARY OBJECTIVES: I. To evaluate the efficacy of ARX788 monotherapy in participants with HER2-low locally advanced unresectable or metastatic breast cancer (MBC) as measured by duration of response (DOR), best overall response (BOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). II. To evaluate the safety of ARX788 monotherapy in participants with HER2-low locally advanced unresectable or MBC. III. To evaluate the safety, tolerability, adherence, and feasibility of the eye toxicity prevention regimen in the ocular toxicity prevention sub study. IV. To evaluate the efficacy of the eye toxicity prevention regimen in the ocular toxicity prevention sub study. EXPLORATORY OBJECTIVES: I. Biomarker analyses to evaluate association of efficacy measures with potential biomarkers (e.g., via assessment of circulating tumor deoxyribonucleic acid (ctDNA), single cell ribonucleic acid (RNA) sequencing, etc.). II. Patient-reported outcomes (PROs) of patients on ARX788 monotherapy. III. To determine the pharmacokinetics (PK) of ARX788 in tears. OUTLINE: Participants are assigned to cohorts based on breast cancer subtype and receive ARX788 intravenously (IV) over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. The first 5 participants successfully enrolled will receive topical amiloride 0.1% to evaluate early safety, tolerability, adherence, and feasibility data. Participants may continue study treatment until progressive disease, intolerable side effects, discontinuation due to Investigator's clinical judgment, discontinuation due to patient's choice, or the Sponsor-investigator's decision to stop the study. After completion of study treatment, participants are followed up at 30 days and then every 12 weeks for 1 year.
研究者
Laura Huppert, MD, BA
Principal Investigator
University of California, San Francisco
入排标准
入选标准
- •Male or female participants age 18 years or greater with ability to provide written informed consent for the study.
- •Eastern Cooperative Oncology Group (ECOG) score of 0-
- •Estimated life expectancy of at least at 6 months per investigator assessment.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Pathologically documented HER2-low locally advanced unresectable or metastatic breast cancer (MBC). NOTE: human epidermal growth factor receptor 2 (HER2)-low status determined by HER2 immunohistochemistry (IHC) 1+ or 2+ and no evidence of HER2 gene amplification by in situ hybridization (ISH)/fluorescence in situ hybridization (FISH), which can be documented from any tumor sample during the patient's cancer treatment history (early-stage or metastatic).
- •Cohort 1: Participants with hormone receptor positive (HR+)/HER2-low locally advanced unresectable or MBC. HR+ status defined as estrogen receptor \>= 10% and/or progesterone receptor ≥ 10% and HER2 low.
- •Cohort 2: Participants with hormone receptor negative (HR-)/HER2-low locally advanced unresectable or MBC. Considered HR- if estrogen receptor (ER) and progesterone receptor (PR) \< 10% and HER2-low.
- •Presence of at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.
- •NOTE: Participant's with at least one measurable lytic bone lesion are eligible.
- •Availability of tumor block or formalin-fixed paraffin-embedded (FFPE) tissue as 10 precut unstained slides will be collected for the HER2 status evaluation and biomarker analysis based on the most recent tumor tissue sample. NOTE: New pretreatment biopsy tissue is preferred as HER2 status may change, but a fresh biopsy is not required. The study team and investigator will make every attempt to get archival tissue. Participants who do not have archival or new tumor tissue available may be eligible after discussion with the study principal investigator (PI).
排除标准
- •Has a prior history of treatment with ARX-788 or auristatin analogues.
- •Has a history of allergic reaction to any component of ARX
- •Has exposure to any other investigational or commercial anti-cancer agents or therapies administered with the intention to treat malignancy within 14 days before the first dose of study treatment. NOTE: Anti-hormonal therapy may be administered up to 7 days prior to the first dose of study treatment.
- •Radiotherapy outside of the brain administered \<7 days prior to first dose of ARX788
- •Prior or current history of interstitial lung disease (ILD), pneumonitis, or other clinically significant lung disease with the exception of disease that is directly attributable to the presence of lung metastases from their underlying cancer.
- •Participants with significant pulmonary conditions, defined as any of the following:
- •Any prior history of drug-induced immune-mediated pneumonitis.
- •Prior history of radiation therapy to the chest of \> 18 gray (Gy) with residual sequelae considered clinically significant by investigator assessment.
- •Radiographic evidence of radiation fibrosis involving \> 15% of the lung parenchyma associated with clinical symptoms.
- •Any requirement for supplemental oxygen.
研究组 & 干预措施
Cohort 2: HR-/HER2-low
Participants with confirmed HR negative (HR-)/human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: ARX788
Cohort 2: HR-/HER2-low
Participants with confirmed HR negative (HR-)/human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: Computed Tomography (CT)
Ocular Toxicity Prevention Sub-study
The first 5 participants from Cohorts 1 and 2 will be given outpatient eye drops to use from home in conjunction with ARX788. Participants will be drop applied to each eye 4 times a day starting on the day of first infusion and continuing daily throughout treatment and for 30 days after the last infusion.
干预措施: Computed Tomography (CT)
Cohort 1: HR+/HER2-low
Participants with locally advanced, unresectable MBC that is hormone receptor (HR) positive (HR+) /human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: Biospecimen Collection
Ocular Toxicity Prevention Sub-study
The first 5 participants from Cohorts 1 and 2 will be given outpatient eye drops to use from home in conjunction with ARX788. Participants will be drop applied to each eye 4 times a day starting on the day of first infusion and continuing daily throughout treatment and for 30 days after the last infusion.
干预措施: Biospecimen Collection
Ocular Toxicity Prevention Sub-study
The first 5 participants from Cohorts 1 and 2 will be given outpatient eye drops to use from home in conjunction with ARX788. Participants will be drop applied to each eye 4 times a day starting on the day of first infusion and continuing daily throughout treatment and for 30 days after the last infusion.
干预措施: Amiloride
Cohort 1: HR+/HER2-low
Participants with locally advanced, unresectable MBC that is hormone receptor (HR) positive (HR+) /human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: Computed Tomography (CT)
Cohort 2: HR-/HER2-low
Participants with confirmed HR negative (HR-)/human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: Biospecimen Collection
Cohort 1: HR+/HER2-low
Participants with locally advanced, unresectable MBC that is hormone receptor (HR) positive (HR+) /human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo CT, PET/CT, and collection of blood samples throughout the study.
干预措施: ARX788
Ocular Toxicity Prevention Sub-study
The first 5 participants from Cohorts 1 and 2 will be given outpatient eye drops to use from home in conjunction with ARX788. Participants will be drop applied to each eye 4 times a day starting on the day of first infusion and continuing daily throughout treatment and for 30 days after the last infusion.
干预措施: ARX788
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 1 year
Objective response rate (ORR) is defined as the proportion of participants who experience complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The ORR and corresponding two-sided exact 90% confidence intervals will be reported.
次要结局
- Duration of response (DOR)(Up to 1 year)
- Overall Best Response (BOR)(Up to 1 year)
- Disease Control Rate (DCR)(Up to 1 year)
- Median Progression Free Survival (PFS)(Up to 2 years)
- Proportion of participants with treatment-emergent adverse events (AEs)(Up to 1 year)
- Percentage of participants adhering to the eye drop(Up to 1 year)
- Median Overall Survival (OS)(Up to 2 years)
- Mean score on an eye pain scale(Up to 1 year)
- Proportion of participants reporting ocular adverse events(Up to 1 year)