Clinical trial NCT02264613: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lymphoma
Peripheral T-Cell Lymphoma
Lead sponsor: Aileron Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
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
timeFrame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
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
timeFrame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
measure: Determine the maximum tolerated dose (MTD) - Phase 1
timeFrame: From the first dose until the end of the first cycle (each cycle is 28 days)
measure: Determine Overall Response Rate - Phase 2
timeFrame: 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:
measure: Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
timeFrame: 8 weeks
measure: Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
timeFrame: 8 weeks
measure: Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
timeFrame: 8 weeks
measure: Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response
timeFrame: 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
measure: Assess additional pharmacologic properties, including biomarkers and immunogenicity
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Duarte
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
Study officials:
References:
citation: Zhou X, Singh M, Sanz Santos G, Guerlavais V, Carvajal LA, Aivado M, Zhan Y, Oliveira MMS, Westerberg LS, Annis DA, Johnsen JI, Selivanova G. Pharmacologic Activation of p53 Triggers Viral Mimicry Response Thereby Abolishing Tumor Immune Evasion and Promoting Antitumor Immunity. Cancer Discov. 2021 Dec 1;11(12):3090-3105. doi: 10.1158/2159-8290.CD-20-1741.