A Phase 1/2a Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone or in Combination in Patients With Advanced Solid Tumors or Lymphomas Expressing Wild-Type p53 Protein
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 13
- 主要终点
- Evaluate the Safety and Tolerability of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas With Wild-type (WT) TP53 Who Are Refractory to or Intolerant of Standard Therapy, or for Whom no Standard Therapy Exists
研究概览
简要总结
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.
详细描述
Open label, multi center, Phase 1 (dose escalation) and Phase 2a (dose expansion) study design to evaluate safety, tolerability, PK, PD and anti-tumor effects of ALRN-6924, alone or in combination with palbociclib, in patients with advanced solid tumors or lymphomas with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt the interaction between the p53 tumor suppressor protein and its predominant endogenous inhibitors, murine double minute 2 (MDM2) and murine double minute X (MDMX).
The Phase 1 portion of the study will enroll adults with histologically or cytologically confirmed malignancies that are metastatic or unresectable and for which standard treatment(s) are not available or are no longer effective. The Phase 2a portion of the study consists of separate cohorts that will enroll distinct groups of patients with specific solid tumors and/or lymphomas to further investigate the clinical safety profile and potential efficacy of ALRN-6924 alone or in a combination regimen.
Treatment will continue until unacceptable toxicity, patient or physician decision to discontinue therapy or disease progression that is either symptomatic, rapidly progressive, requires urgent intervention or is associated with a decline in performance status.
Patients with PTCL have been selected as a group to be further studied in Phase 2a.
Patients with MDM2-amplified or MDM2/CDK4-co-amplified solid tumors have been selected as another group to be further studied in Phase 2a.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically or cytologically confirmed solid tumor or lymphoma that is not amenable to standard therapies.
- •Cohort specific biomarkers, including confirmed or anticipated WT TP53 (Phase 1 and PTCL expansion cohorts) and MDM2-amplification or MDM2/CDK4-co-amplification (solid tumor expansion cohort)
- •At least one target lesion that is measurable by RECIST 1.1, RANO or IWG 2014, as appropriate for tumor type
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-1
- •Adequate coagulation and hematologic function
- •Adequate hepatic and renal function
- •Sufficient wash out from prior therapies and recovery from all significant acute toxicities
排除标准
- •Prior treatment with an MDM2 inhibitor, with protocol specified exceptions
- •Known hypersensitivity to any study drug component
- •Protocol specified cardiovascular risk factors
- •Clinically significant gastrointestinal bleeding within 6 months
- •Clinically significant third-space fluid accumulation
- •Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
- •HPV positive tumors
- •Second malignancy within two years, with protocol specified exceptions
- •Pregnancy or lactation
研究组 & 干预措施
Dose Regimen A (DR-A)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
干预措施: ALRN-6924 (Drug)
Dose Regimen B (DR-B)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
干预措施: ALRN-6924 (Drug)
Dose Regimen C (DR-C)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle
干预措施: ALRN-6924 (Drug)
Combination with palbociclib
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle Drug: Palbociclib Fixed-dose capsule administered orally on days 1 through 21 of a 28-day cycle
干预措施: ALRN-6924 (Drug)
结局指标
主要结局
Evaluate the Safety and Tolerability of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas With Wild-type (WT) TP53 Who Are Refractory to or Intolerant of Standard Therapy, or for Whom no Standard Therapy Exists
时间窗: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Evaluate the Safety and Tolerability of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas With Wild-type (WT) TP53 Who Are Refractory to or Intolerant of Standard Therapy, or for Whom no Standard Therapy Exists, Expansion
时间窗: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Determine the Maximum Tolerated Dose (MTD) of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas
时间窗: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
Determine the maximum tolerated dose (MTD)
Determine Overall Response Rate
时间窗: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
The proportion of efficacy-evaluable patients who achieve complete response (CR) or partial response (PR), per investigator assessment, in accordance with RECIST 1.1 or iRECIST (for solid tumor patients) or Response Assessment in Neuro-Oncology (RANO) criteria (for glioblastoma patients).
次要结局
- Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response(From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days)
- Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas(8 weeks)