A Phase 1/2, First-in-Human, Open-label, Dose Escalation Study of GB1275 Monotherapy and in Combination With an Anti-PD-1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma, Followed by Basket Expansion of GB1275 With Standard of Care or in Combination With an Anti-PD-1 Antibody in Patients With Specified Metastatic Solid Tumors
概览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
- 入组人数
- 61
- 试验地点
- 8
- 主要终点
- Phase 1 Dose Escalation - Regimens A, B,and C: Incidence of dose limiting toxicities (DLTs)
概览
简要总结
This first-in-human (FIH ) study is an open-label, multicenter study that consists of a Phase 1 Dose Escalation/Expansion phase of GB1275 monotherapy or in combination with Anti-PD-1 Antibody or in combination with Standard of Care in Patients with Metastatic Pancreatic Adenocarcinoma followed by a Phase 2 Basket Expansion phase in Patients with Specified Metastatic Solid Tumors
详细描述
Note: The Phase 2 portion of the study was not initiated.
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
- •Subject has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Women of childbearing potential must use an acceptable method of contraception
- •Subjects with the the following:
- •Regimen A and B:
- •pancreatic adenocarcinoma,
- •esophageal adenocarcinoma, or esophageal squamous cell carcinoma, or
- •gastric/gastroesophageal junction adenocarcinoma, or
- •prostate cancer, or
- •colorectal adenocarcinoma, or subjects with tumor types that have progressed after receiving initial treatment benefit rom the last single agent checkpoint inhibitor that is approved for the indication or in combination with standard of care therapy, for example, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, renal cell carcinoma, and hepatocellular carcinoma, etc.
- •Regimen C: newly diagnosed stage IV pancreatic cancer
排除标准
- •History of another malignancy within 2 years prior to first study drug(s) administration, unless the malignancy was treated with curative intent and the likelihood of relapse is \<5% in 2 years
- •Pregnant or nursing
- •Known history of testing positive for human immunodeficiency virus (HIV)
- •Gastrointestinal (GI) tract disease causing the inability to take oral medication.
- •Positive test for Hepatitis B virus surface antigen (HBsAg) or a and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
- •Other protocol-defined inclusion/exclusion criteria will apply
研究组 & 干预措施
Phase 1: Regimen A - GB1275 monotherapy
GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID).
干预措施: GB1275 (Drug)
Phase 1: Regimen B - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab dose escalation and expansion:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: GB1275 (Drug)
Phase 1: Regimen B - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab dose escalation and expansion:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: pembrolizumab (Drug)
Phase 1: Regimen C - GB1275 with Standard of Care (SOC)
GB1275 with SOC dose escalation:
GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI)
干预措施: GB1275 (Drug)
Phase 1: Regimen C - GB1275 with Standard of Care (SOC)
GB1275 with SOC dose escalation:
GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI)
干预措施: nab-paclitaxel and gemcitabine (Drug)
Phase 2: Cohort 1 - GB1275 with SOC
GB1275 with SOC Basket Cohort in patients with newly diagnosed metastatic pancreatic cancer:
GB1275 oral administration; twice per day (BID) and nab-paclitaxel and gemcitabine per USPI.
干预措施: GB1275 (Drug)
Phase 2: Cohort 1 - GB1275 with SOC
GB1275 with SOC Basket Cohort in patients with newly diagnosed metastatic pancreatic cancer:
GB1275 oral administration; twice per day (BID) and nab-paclitaxel and gemcitabine per USPI.
干预措施: nab-paclitaxel and gemcitabine (Drug)
Phase 2: Cohort 2 - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab Basket Cohort in patients with MSS colorectal cancer:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: GB1275 (Drug)
Phase 2: Cohort 2 - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab Basket Cohort in patients with MSS colorectal cancer:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: pembrolizumab (Drug)
Phase 2: Cohort 3 - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab Basket Cohort in patients with gastric/GEJ cancer, PD-L1 positive:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: GB1275 (Drug)
Phase 2: Cohort 3 - GB1275 with an Anti-PD-1
GB1275 with pembrolizumab Basket Cohort in patients with gastric/GEJ cancer, PD-L1 positive:
GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Phase 1 Dose Escalation - Regimens A, B,and C: Incidence of dose limiting toxicities (DLTs)
时间窗: Regimen A and B dose escalation Days 1-21, Regimen C dose escalation Days 8-36 days
Phase 1 Dose Escalation - Regimens A, B, and C and Phase 1 Expansion - Regimen B: Incidence of adverse events (AEs)
时间窗: Regimen A and C from first dose through 30 days post last dose, Regimen B from first dose through 90 days post last dose
Phase 1 Dose Escalation - Regimens A and B: Cmax of GB1275
时间窗: From first dose through 30 days post last dose
Maximum observed plasma concentration
Phase 1 Dose Escalation - Regimens A and B: Ctrough of GB1275
时间窗: From first dose through 30 days post last dose
Trough observed plasma concentration
Phase 1 Dose Escalation - Regimens A and B: Tmax of GB1275
时间窗: From first dose through 30 days post last dose
Time of maximum observed plasma concentration
Phase 1 Dose Escalation - Regimens A and B: AUC of GB1275
时间窗: From first dose through 30 days post last dose
Area under the plasma concentration-time curve
Phase 1 Dose Escalation - Regimens A and B: t1/2 of GB1275
时间窗: From first dose through 30 days post last dose
Terminal phase elimination half-life
Phase 1 Dose Escalation - Regimens A and B: CL/F of GB1275
时间窗: From first dose through 30 days post last dose
Oral clearance
Phase 2 - Basket Cohorts 1, 2 and 3: Objective Response Rate (ORR)
时间窗: 24 months
ORR defined as the proportion of subjects with best overall confirmed response (BOCR) of either a complete response (CR) or partial response (PR) as assessed by the Investigator based on RECIST v1.1
次要结局
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275(From first dose through 30 days post last dose)
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275(From first dose through 30 days post last dose)
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: CL/F of GB1275(From first dose through 30 days post last dose)
- Phase 1 - Regimen C: Cmax of nab-paclitaxel and gemcitabine(From first dose through 30 days post last dose)
- Phase 1 - Regimen C: Tmax of nab-paclitaxel and gemcitabine)(From first dose through 30 days post last dose)
- Phase 1 - Regimen C: AUC of nab-paclitaxel and gemcitabine(From first dose through 30 days post last dose)
- Phase 2 - Basket Cohorts 1, 2, and 3: Duration of Response (DOR)(24 months)
- Phase 2 - Basket Cohorts 1, 2, and 3: Time to Response (TTR)(24 months)
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275(From first dose through 30 days post last dose)
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275(From first dose through 30 days post last dose)
- Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275(From first dose through 30 days post last dose)
- Phase 2 - Basket Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR)(6 months)
- Phase 2 - Basket Cohorts 1, 2, and 3: Progression Free Survival (PFS)(24 months)
- Phase 2 - Basket Cohorts 1, 2, and 3: Time to Progression (TTP)(24 months)
- Phase 2 - Basket Cohorts 1, 2, and 3: Overall Survival (OS)(24 months)
- Phase 2 - Basket Cohorts 1, 2, and 3: Incidence of AEs(Basket Cohorts 1 from first dose through 30 days post last dose, Basket Cohorts 2 and 3 from first dose through 90 days post last dose.)
- Phase 2 - Basket Cohort 1, 2 and 3: PK profile of GB1275(Basket Cohorts 1, 2, and 3 from first dose through 30 days post last dose.)