ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas
- Registration Number
- NCT02264613
- Lead Sponsor
- Aileron Therapeutics, Inc.
- Brief Summary
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 149
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Regimen A (DR-A) ALRN-6924 Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle. Dose Regimen C (DR-C) ALRN-6924 Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle Combination with palbociclib ALRN-6924 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 Dose Regimen B (DR-B) ALRN-6924 Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
- Primary Outcome Measures
Name Time Method Determine the maximum tolerated dose (MTD) - Phase 1 From the first dose until the end of the first cycle (each cycle is 28 days) Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with advanced solid tumors or lymphomas
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 - Phase 1 From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 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 - Phase 2 From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days) Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Determine Overall Response Rate - Phase 2 From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months 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).
- Secondary Outcome Measures
Name Time Method Assess additional pharmacologic properties, including biomarkers and immunogenicity Up to 24 weeks The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas 8 weeks Time of Peak Plasma Concentration (Tmax)
Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months 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).