A Phase 1 Dose Escalation and Expansion Study of EO-3021, an Anti-claudin 18.2 (CLDN18.2) Antibody Drug Conjugate, in Patients With Solid Tumors Likely to Express CLDN18.2
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 88
- 试验地点
- 18
- 主要终点
- Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
研究概览
简要总结
This study is an open-label, international, multi-center, Phase 1 study in adult patients with solid tumors likely to express CLDN18.2.
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
- •Availability of tumor tissue for evaluation of biomarker
- •Patients enrolled to expansion must have tumors expressing CLDN 18.2 based on central prospective IHC testing.
- •Histologically and/or cytologically confirmed diagnosis of advanced metastatic gastric/GEJ adenocarcinoma not amenable to resection or radiation therapy with curative intent
- •≥ 18 years of age
- •ECOG performance status (PS) 0 or 1 at Screening
- •Progressed on or after standard therapy, or are intolerable of available standard therapy, or there is no available standard therapy
- •In dose escalation, there is no limit on the number of prior lines of therapy.
- •In expansion, for EO-3021 monotherapy, at least 1 but no more than 3 prior lines of therapy in the advanced/metastatic setting is allowed
- •In expansion, for EO-3021 in combination with ramucirumab, only 1 prior line of therapy in the advanced/metastatic setting is allowed. Prior fluoropyrimidine and platinum-containing chemotherapy is required
- •In expansion, for EO-3021 in combination with dostarlimab, no prior systemic therapy in the advanced/metastatic setting is allowed.
- •Have at least one measurable extra-cranial lesion as defined by RECIST v1.1
- •Adequate organ function
- •Life expectancy > 12 weeks
- •Ability to understand the nature of this study, comply with protocol requirements, and give written informed consent
- •Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 6 months following study completion (or longer if required by local regulation)
排除标准
- •Pregnant or breastfeeding
- •Symptomatic or untreated brain metastases
- •Have previously received CLDN18.2 antibody drug conjugates (ADCs) or any ADC containing an auristatin payload (prior monoclonal antibody against CLDN18.2 may be eligible)
- •Have peripheral neuropathy Grade ≥2
- •Have history of non-infectious pneumonitis/interstitial lung disease
- •Have diagnosis of another malignancy, or history of systemic treatment for invasive cancer within last 3 years. Note: Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. Diagnosis of non-melanoma skin cancer, carcinoma in situ of the cervix or breast, or noninvasive tumor does not affect eligibility
- •Have active ocular surface disease at baseline (based on screening ophthalmic examination) as defined as symptomatic or Grade ≥2 disease involving the cornea
- •Have history of Grade ≥2 gastritis
- •Have serious concurrent illness or clinically relevant active bacterial, fungal or viral infection
- •Have a history of several allergic and/or anaphylactic reactions to known chimeric, human, or humanized antibodies, fusion proteins or known allergies to components of EO-3021, ramucirumab, or dostarlimab
- •Clinically significant cardiac disease, including but not limited to symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 6 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
- •Have history of allogenic hematopoietic stem cell transplantation or solid organ transplantation with ongoing systemic immunosuppressive therapy
- •Received any live vaccine within 30 days of enrollment
- •Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the Investigator
- •Expansion only: Have HER2+ disease as defined by American Society of Clinical Oncology-College of American Pathologists guidelines for gastric/GEJ adenocarcinoma
- •Ramucirumab Arms Only: Received prior treatment with ramucirumab and other VEGFR2 inhibitors
- •Dostarlimab Arms Only: Prior treatment with immune checkpoint inhibitors (ICI) including dostarlimab and other anti-PD-1, anti-PD-L1, etc.
研究组 & 干预措施
EO-3021 Monotherapy
In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 monotherapy at various doses every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have received one and no more than three lines of prior systemic therapy in the advanced metastatic setting will be randomized to one of two doses of EO-3021 dosed every 3 weeks to confirm RP2D.
干预措施: EO-3021 (Drug)
EO-3021 in combination with ramucirumab
In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with ramucirumab every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have received only one prior systemic therapy in the advanced metastatic setting will be treated with EO-3021 in combination with ramucirumab every 3 weeks to confirm RP2D.
干预措施: EO-3021 (Drug)
EO-3021 in combination with ramucirumab
In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with ramucirumab every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have received only one prior systemic therapy in the advanced metastatic setting will be treated with EO-3021 in combination with ramucirumab every 3 weeks to confirm RP2D.
干预措施: Ramucirumab (CYRAMZA®) (Drug)
EO-3021 in combination with dostarlimab
In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with dostarlimab every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have not received any prior systemic therapies in the advanced metastatic setting will be treated with EO-3021 in combination with dostarlimab every 3 weeks to confirm RP2D.
干预措施: EO-3021 (Drug)
EO-3021 in combination with dostarlimab
In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with dostarlimab every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have not received any prior systemic therapies in the advanced metastatic setting will be treated with EO-3021 in combination with dostarlimab every 3 weeks to confirm RP2D.
干预措施: Dostarlimab (Drug)
结局指标
主要结局
Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
时间窗: From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
The Incidence Rate of Dose Limiting Toxicities (DLT) During the First 21-day Cycle of Treatment With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
时间窗: The first 21-day treatment cycle for each patient enrolled in the Escalation Phase
Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
时间窗: From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab
时间窗: From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose
Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
时间窗: From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
The Estimate of Overall Response Rate (ORR) for the Efficacy Population.
时间窗: Up to 24 months
Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1.
次要结局
未报告次要终点