A Phase II Study of Pemigatinib Plus Durvalumab (MEDI4736) in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement
概览
- 阶段
- 2 期
- 干预措施
- Durvalumab
- 疾病 / 适应症
- Intrahepatic Cholangiocarcinoma
- 发起方
- Mehmet Akce
- 入组人数
- 38
- 试验地点
- 3
- 主要终点
- Confirmed objective response rate (ORR)
- 状态
- 招募中
- 最后更新
- 24天前
概览
简要总结
This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic cholangiocarcinoma. Each cycle will be 3 weeks. Pemigatinib is administered at 13.5 mg orally daily 2 weeks on and 1 week off. Durvalumab is administered at 1500 mg intravenously once every 3 weeks. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur every 9 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months (about 35 cycles) of pemigatinib and durvalumab treatment from Cycle 1 Day 1 is allowed.
研究者
Mehmet Akce
Sponsor-Investigator
Hoosier Cancer Research Network
入排标准
入选标准
- •Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0 or
- •Body weight of \> 30 kg.
- •Histologically diagnosed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR-2 fusion or rearrangement detected by Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus, Guardant 360 or other platforms of next generation sequencing will be allowed). AJCC, 8th edition. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
- •Measurable disease according to RECIST 1.
- •Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Have received gemcitabine cisplatin and durvalumab or another anti-PD-1 Ab for unresectable locally advanced or metastatic cholangiocarcinoma with either disease progression, intolerance to cytotoxic chemotherapy, or have received at least 6 months of therapy with stable disease or partial response. Prior neoadjuvant or adjuvant therapy is permitted if documented disease recurrence occurred ≥ 6 months after the last date of neoadjuvant or adjuvant therapy.
- •Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
- •Absolute Neutrophil Count (ANC): ≥1500/µL
排除标准
- •Prior therapy with a FGFR inhibitor.
- •Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination
- •History of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
- •Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided.
- •History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
- •Participation in another clinical study with an investigational product during the last 3 months
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 28 days prior to the first dose of study regimen. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by sponsor-investigator.
- •Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- •Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
研究组 & 干预措施
Pemigatinib + Durvalumab
Pemigatinib 13.5 mg will be taken orally at the same time each day for 14 days (Day 1 through Day 14), followed by 7 days off treatment (Day 15 through Day 21) of each 21 day cycle. Durvalumab 1500 mg IV will be administered every 3 weeks on Day 1 of each 21-day cycle.
干预措施: Durvalumab
Pemigatinib + Durvalumab
Pemigatinib 13.5 mg will be taken orally at the same time each day for 14 days (Day 1 through Day 14), followed by 7 days off treatment (Day 15 through Day 21) of each 21 day cycle. Durvalumab 1500 mg IV will be administered every 3 weeks on Day 1 of each 21-day cycle.
干预措施: Pemigatinib
结局指标
主要结局
Confirmed objective response rate (ORR)
时间窗: 24 months
ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1. A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
次要结局
- Progression Free Survival (PFS)(24 months)
- Disease Control Rate (DCR)(24 months)
- Overall Survival(24 months)
- Duration of response(24 months)
- Number of Participants with Adverse Events(24 months)