Brief Summary
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.
Brief Title
ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Solid Tumor
Lymphoma
Peripheral T-Cell Lymphoma
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02264613
Org Class
Industry
Org Full Name
Aileron Therapeutics, Inc.
Org Study Id
ALRN-6924-1-01
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Outcome 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
Outcome Time Frame
From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Outcome Description
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Outcome 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 2
Outcome Time Frame
From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Outcome Description
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
Outcome Measure
Determine the maximum tolerated dose (MTD) - Phase 1
Outcome Time Frame
From the first dose until the end of the first cycle (each cycle is 28 days)
Outcome 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).
Outcome Measure
Determine Overall Response Rate - Phase 2
Outcome 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
Secondary Outcomes
Outcome Description
Peak Plasma Concentration (Cmax)
Outcome Time Frame
8 weeks
Outcome Measure
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
Outcome Description
Area under the plasma concentration versus time curve (AUC)
Outcome Time Frame
8 weeks
Outcome Measure
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
Outcome Description
Time of Peak Plasma Concentration (Tmax)
Outcome Time Frame
8 weeks
Outcome Measure
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
Outcome 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).
Outcome 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
Outcome Measure
Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response
Outcome Description
The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Assess additional pharmacologic properties, including biomarkers and immunogenicity
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
LYMPHOMA
LYMPHOMA, T-CELL, PERIPHERAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
LYMPHOMA, T-CELL
LYMPHOMA, NON-HODGKIN