A Phase 1/2 Study of PRO1107 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Genmab
- 入组人数
- 33
- 试验地点
- 11
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
This is a global, open-label, multicenter Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of GEN1107 (PRO1107) in participants with advanced solid tumors. This study consists of 2 parts, Part A: dose escalation and dose level expansion, and Part B: tumor specific expansion.
详细描述
This is a Phase 1/2 study of GEN1107, a protein tyrosine K 7 (PTK7) targeted antibody-drug conjugate (ADC), to evaluate the safety, tolerability, PK, and antitumor activity of GEN1107 in participants with advanced solid tumors, including ovarian cancer, endometrial cancer, triple negative breast cancer, non-small cell lung cancer, gastroesophageal cancer, and urothelial cancer. This study consists of 2 parts, Part A: Dose Escalation and Dose Level Expansion and Part B: Tumor Specific Expansion.
In Part A, GEN1107 will be administered in different dosing regimens via intravenous (IV) infusion.
Part B will be initiated at a dose level based on a comprehensive analysis of safety, tolerability, clinical PK, pharmacodynamics (PD) and activity data from Part A in up to 4 different tumor-specific cohorts of up to 40 participants per cohort.
Participants will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Pathologically confirmed diagnosis of one of the following tumor types:
- •Ovarian cancer (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer)
- •Endometrial cancer (any subtype excluding sarcoma)
- •Triple negative breast cancer (TNBC)
- •Non-small cell lung cancer (NSCLC)
- •Metastatic or unresectable locally advanced, recurrent, disease not amenable to further local therapy following prior systemic therapies known to confer clinical benefit.
- •Participants must have a histologically or cytologically confirmed metastatic or unresectable solid malignancy as specified below:
- •Ovarian cancer
- •Endometrial cancer
- •Measurable disease at baseline as defined per RECIST, Version 1.1
排除标准
- •Prior treatment with anti-PTK7-directed therapy.
- •Had progressive disease as best response while on treatment with an auristatin (eg, a vedotin or pelidotin)- based ADC as the most recent line of therapy.
- •History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] ≥90%)
- •Known active central nervous system metastases, including carcinomatous meningitis. Participants with brain metastases may participate provided the metastases have been treated and are stable for at least 4 weeks prior to the first dose of study drug, they have no new or enlarging brain metastases and have discontinued corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug. Participants with a history of brain metastases, suspected new brain metastases, or a diagnosis of NSCLC or breast cancer should have a computed tomography (CT)/ magnetic resonance imaging (MRI) scan of the brain at screening.
- •Participants with active or chronic corneal disorders, history of corneal transplantation, or any clinically significant corneal disease that prevents adequate monitoring of potential drug-induced keratopathy. Note: Participants with other active ocular conditions requiring ongoing therapy and/or monitoring must be discussed with the sponsor prior to enrollment.
- •Additional protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
GEN1107
GEN1107 monotherapy in escalating doses in Part A and at the dose level in Part B.
干预措施: GEN1107 (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: Through end of treatment, up to approximately 1 year
Type, incidence, severity, seriousness, and relatedness of adverse events.
Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to a maximum of Day 28
Incidence of dose limiting toxicities.
次要结局
- Disease Control Rate(Through end of treatment, up to approximately 1 year)
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for GEN1107(Varying timepoints through end of treatment, up to approximately 1 year)
- Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for GEN1107(Varying timepoints through end of treatment, up to approximately 1 year)
- Pharmacokinetic Parameter Trough Concentration (Ctrough) for GEN1107(Varying timepoints through end of treatment, up to approximately 1 year)
- Number of Participants with Anti-drug Antibodies (ADAs)(Varying timepoints through end of treatment, up to approximately 1 year)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) for GEN1107(Varying timepoints through end of treatment, up to approximately 1 year)
- Progression-free Survival(Up to approximately 18 months)
- Cancer Antigen 125 (CA-125) Response per Gynecological Cancer Intergroup (GCIG) Criteria for Ovarian Cancer(Varying timepoints through end of treatment, up to approximately 1 year)
- Objective Response Rate(Through end of treatment, up to approximately 1 year)
- Duration of Objective Response(From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months)
- Pharmacokinetic Parameter Area Under the Curve (AUC) for GEN1107(Varying timepoints through end of treatment, up to approximately 1 year)