A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 31
- 试验地点
- 10
- 主要终点
- Number of participants with AEs leading to study treatment discontinuation
研究概览
简要总结
Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab (MGD019). The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, metastatic castration-resistant prostate cancer (mCRPC), melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled.
Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years.
Tumor assessments are performed every 8 weeks (± 7 days) for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD).
Participants will be followed for safety throughout the study. .
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
- •1. Ability to provide and document informed consent and willing and able to comply with all study procedures.
- •Participants diagnosed with advanced solid tumors including but not limited to metastatic castration-resistant prostate cancer, melanoma, pancreatic cancer, hepatocellular carcinoma, ovarian cancer and renal cell carcinoma.
- •Participants have received approved therapies according to their diagnosis.
- •Participants must have an available tumor tissue sample. A fresh tumor biopsy may be performed if no archival sample is available.
- •Eastern Cooperative Oncology Group performance status of less than or equal to
- •Life expectancy of at least 12 weeks.
- •Evidence of measurable tumor for evaluation
- •Acceptable end organ function according to laboratory results.
- •Patients must agree to use highly-effective contraception during the study, and not donate sperm or ova.
排除标准
- •Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
- •Another malignancy that required treatment within the past 2 years. Participants who have had curative therapy for non-melanomatous skin cancer, localized prostate cancer (Gleason score < 6), or carcinoma in situ are eligible for the study.
- •Active viral, bacterial, or fungal infection requiring systemic treatment within 1 week of initiation of study drug. Participants are eligible after SARS CoV 2-related symptoms have fully recovered for ≥ 72 hours.
- •History of immunodeficiency. Participants with HIV are eligible if they have a CD4+ count ≥ 300/µL, undetectable viral load, and maintained on antiretroviral therapy for a minimum of 4 weeks.
- •Prior autologous/allogeneic stem cell or tissue/solid organ transplant
- •Prior treatment with MGD009, enoblituzumab, or other B7-H3 targeted agents for cancer.
- •Clinically significant cardiovascular disease, lung compromise, venous insufficiency, or gastrointestinal disorders.
- •Participants with greater than Grade 1 peripheral neuropathy.
- •Participants who have a history of severe adverse events (AEs) from immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or CTLA-4 inhibitors). All other AEs from prior immune checkpoint inhibitors must be resolved to Grade 1 or less. Participants with any grade neurologic toxicity from prior immune checkpoint inhibitors are excluded.
- •Pleural effusion or ascites. Trace pleural or peritoneal fluid is not exclusionary.
- •History of Guillain-Barre syndrome, myasthenia gravis, or other autoimmune sensory or motor neuropathies.
研究组 & 干预措施
Cohort -1
vobramitamab duocarmazine at dose level -1 and lorigerlimab intravenously (IV) every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort -1
vobramitamab duocarmazine at dose level -1 and lorigerlimab intravenously (IV) every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort 1
vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort 1
vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort 2
vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort 2
vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort 3
vobramitamab duocarmazine at dose level 2 and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort 3
vobramitamab duocarmazine at dose level 2 and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort 4
vobramitamab duocarmazine at dose level 3 and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort 4
vobramitamab duocarmazine at dose level 3 and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort 5
vobramitamab duocarmazine at dose level 4 and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort 5
vobramitamab duocarmazine at dose level 4 and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
Cohort Expansion
maximum tolerated dose of vobramitamab duocarmazine and lorigerlimab IV every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Cohort Expansion
maximum tolerated dose of vobramitamab duocarmazine and lorigerlimab IV every 4 weeks
干预措施: lorigerlimab (Biological)
结局指标
主要结局
Number of participants with AEs leading to study treatment discontinuation
时间窗: Up to 2 years
Number of participants with adverse events (AEs)
时间窗: Up to 2 years
Number of participants with serious adverse events (SAEs)
时间窗: Up to 2 years
次要结局
- Mean maximum observed concentration (Cmax) of vobramitamab duocarmazine(Throughout the study, up to 2 years)
- Mean maximum observed concentration (Cmax) of lorigerlimab(Throughout the study, up to 2 years)
- Mean time to maximum concentration (Tmax) of vobramitamab duocarmazine(Throughout the study, up to 2 years)
- Mean time to maximum concentration (Tmax) of lorigerlimab(Throughout the study, up to 2 years)
- Mean area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine(Throughout the study, up to 2 years)
- Mean area under the concentration-time curve during the dosing interval (AUCtau) of lorigerlimab(Throughout the study, up to 2 years)
- Mean trough concentration of vobramitamab duocarmazine(Day 1 of each cycle (every 4 weeks) up to 2 years.)
- Mean trough concentration of lorigerlimab(Throughout the study, up to 2 years)
- Number of participants who develop anti-drug antibodies (ADA) to vobramitamab duocarmazine(Throughout the study, up to 2 years)
- Number of participants who develop ADA to lorigerlimab(Throughout the study, up to 2 years)
- Objective response rate (ORR)(Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.)
- Median progression free survival (PFS)(Assessed every 8 weeks for the first 6 months, then every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years.)
- Median duration of response (DoR)(Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.)
- Median overall survival (OS)(Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years)
- Median radiographic PFS (rPFS) for mCRPC(Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.)
- Prostate-specific antigen (PSA) response rate for mCRPC(PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.)
- Best PSA percent change from baseline for mCRPC(PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.)
- Median time to PSA progression for mCRPC(PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.)
- Median duration of PSA response for mCRPC(PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.)