Description:
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid
tumors or lymphomas with WT TP53.
Title
- Brief Title: ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
ALRN-6924-1-01
- NCT ID:
NCT02264613
Conditions
- Solid Tumor
- Lymphoma
- Peripheral T-Cell Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| ALRN-6924 | | Combination with palbociclib |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose Regimen A (DR-A) | Experimental | Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle. | |
| Dose Regimen B (DR-B) | Experimental | Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle | |
| Dose Regimen C (DR-C) | Experimental | Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle | |
| Combination with palbociclib | Experimental | 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 | |
Eligibility Criteria
Inclusion Criteria
- 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
Key Exclusion Criteria
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Time Frame: | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days) |
| Safety Issue: | |
| Description: | Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0 |
Secondary Outcome Measures
| Measure: | Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas |
| Time Frame: | 8 weeks |
| Safety Issue: | |
| Description: | Peak Plasma Concentration (Cmax) |
| Measure: | Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas |
| Time Frame: | 8 weeks |
| Safety Issue: | |
| Description: | Area under the plasma concentration versus time curve (AUC) |
| Measure: | Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas |
| Time Frame: | 8 weeks |
| Safety Issue: | |
| Description: | Time of Peak Plasma Concentration (Tmax) |
| Measure: | Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Assess additional pharmacologic properties, including biomarkers and immunogenicity |
| Time Frame: | Up to 24 weeks |
| Safety Issue: | |
| Description: | The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Aileron Therapeutics |
Last Updated
July 14, 2020
