NCT03965845已完成1 期
A Phase 1b/2, Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor Telaglenastat (CB-839) in Combination With CDK4/6 Inhibitor Palbociclib in Patients With Advanced or Metastatic Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 10
- 主要终点
- Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events
研究概览
简要总结
This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor telaglenestat (CB-839) with the CDK4/6 Inhibitor, palbociclib in participants with advanced/metastatic solid tumors.
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
- •Part 1: Have documented incurable/locally advanced or metastatic solid tumors that have either relapsed or are refractory or intolerant to the standard therapies of proven clinical benefit.
- •Part 2: Availability of archival tumor tissue block or slides (Fresh tumor biopsy will be required if archival tissue is not available)
- •Part 2, Cohort 1: Incurable/locally advanced or metastatic KRAS-mutant CRC previously treated with systemic therapy (examples include: oxaliplatin-, irinotecan-and 5 FU-based chemotherapy (unless contraindicated) with or without bevacizumab)
- •Part 2, Cohort 2: Incurable/locally advanced or metastatic KRAS-mutant NSCLC previously treated with systemic chemotherapy including platinum-based and anti-PD-1/PDL-1 therapy (unless contraindicated)
- •Part 2, Cohort 3: Advance KRAS-mutant Pancreatic Ductal Adenocarcinoma (PDAC) harboring a mutation or loss in CDKN2A (PDAC) and received treatment with one or more lines of systemic chemotherapy with FOLFIRINOX and/or gemcitabine/abraxane in the neoadjuvant, adjuvant, or metastatic disease setting or unable to receive standard of care chemotherapy
- •Cohort 4 may be opened only if Cohort 3 achieves predefined criteria for efficacy
- •Part 2 Cohort 4: Advanced KRAS-mutant Pancreatic Ductal Adenocarcinoma (PDAC). · Histological or cytological diagnosis of advanced or metastatic KRAS-mutant with CDKN2A wild type (PDAC) and received treatment with one or more lines of systemic chemotherapy with FOLFIRINOX and/or gemcitabine/abraxane in the neoadjuvant, adjuvant, or metastatic disease setting or unable to receive standard of care chemotherapy.
- •For both Part 1 and 2:
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- •Ability to provide written consent in accordance with federal, local and institutional guidelines
- •PER RECIST v1.1 evaluable disease (for part 1) or measurable disease (for Part 2)
- •Recovery to baseline or to Grade 1 CTCAE v5.0 of toxicities that were related to prior therapies
排除标准
- •Prior treatment with CB-839 or palbociclib
- •Unable to receive oral medication
- •Infection requiring more than 5 days of parenteral antibiotics, antivirals, or antifungals within two weeks prior to C1D1
- •Unable to discontinue proton pump inhibitor use before study treatment
- •Refractory nausea and vomiting, uncontrolled diarrhea, malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes or other situation that may preclude adequate absorption
- •Active and/or untreated central nervous system metastasis. Patients with treated brain metastasis must have (1) documented radiographic stability of at least 4 weeks in duration demonstrating on baseline central nervous system imaging prior to study treatment and (2) be symptomatically stable and off steroids for at least 2 weeks before administration of any study treatment.
- •Major surgery within 28 days prior to first dose of study drug
- •Receipt of any anticancer therapy within the following windows:
- •small molecule TKI therapy (including investigational) within 2 weeks or 5 half-lives prior to expected Cycle 1 Day 1 dose
- •any type of anti-cancer antibody or cytotoxic chemo within 4 weeks prior to Cycle 1 Day 1 Dose
- •radiation therapy for bone metastasis within 2 weeks prior or any other external radiation therapy within 4 weeks prior to C1D1
- •patients with clinically relevant ongoing complications from prior radiation therapy are not eligible
研究组 & 干预措施
Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg
Experimental
干预措施: Telaglenestat (CB-839) (Drug)
Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg
Experimental
干预措施: Palbociclib Oral Capsule or Tablet [Ibrance] (Drug)
Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg
Experimental
干预措施: Telaglenestat (CB-839) (Drug)
Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg
Experimental
干预措施: Palbociclib Oral Capsule or Tablet [Ibrance] (Drug)
Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg
Experimental
干预措施: Telaglenestat (CB-839) (Drug)
Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg
Experimental
干预措施: Palbociclib Oral Capsule or Tablet [Ibrance] (Drug)
Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg
Experimental
干预措施: Telaglenestat (CB-839) (Drug)
Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg
Experimental
干预措施: Palbociclib Oral Capsule or Tablet [Ibrance] (Drug)
Part 2: Expansion
Experimental
The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.
干预措施: Telaglenestat (CB-839) (Drug)
Part 2: Expansion
Experimental
The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.
干预措施: Palbociclib Oral Capsule or Tablet [Ibrance] (Drug)
结局指标
主要结局
Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events
时间窗: Start of treatment to 28 days post treatment
Number of participants with treatment related adverse events as assessed by CTCAE v5.0
Maximum tolerated dose and/or Recommended Phase 2 Dose:
时间窗: Measured from Part 1 patients only within their first 28 day cycle
Incidence and nature of dose-limiting toxicities
次要结局
- Maximum plasma concentration of telaglenastat and palbociclib:(PKs are drawn on two different days (Day 8 and Day 15) during Cycle 1)
- Anti-tumor activity of telaglenestat and palbociclib:(Approximately every 8 weeks until disease progression, for approximately 18 months)
研究者
研究点 (10)
Loading locations...
相似试验
终止
1 期
Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid TumorsSolid TumorTNBC - Triple-Negative Breast CancerColorectal CancerRCCCRCccRCCClear Cell Renal Cell CarcinomaNCT03875313Calithera Biosciences, Inc33
招募中
1 期
A Study of BGB-11417 in Participants With Myeloid MalignanciesAcute Myeloid LeukemiaMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative NeoplasmNCT04771130BeOne Medicines260
已完成
1 期
A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)Bladder CancerNCT05375903UroGen Pharma Ltd.51
招募中
1 期
Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-DegraderB-cell MalignancyNon-Hodgkin LymphomaChronic Lymphocytic Leukemia/Small Lymphocytic LymphomaMarginal Zone LymphomaDLBCL UnclassifiableRichter's TransformationMantle Cell LymphomaFollicular LymphomaWaldenström MacroglobulinemiaNCT05294731BeiGene146
已完成
1 期
Study of Avelumab-M3814 CombinationsOncologySolid TumorsNCT03724890EMD Serono Research & Development Institute, Inc.57