<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02264613</url>
  </required_header>
  <id_info>
    <org_study_id>ALRN-6924-1-01</org_study_id>
    <nct_id>NCT02264613</nct_id>
  </id_info>
  <brief_title>ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aileron Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aileron Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid&#xD;
      tumors or lymphomas with WT TP53.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open label, multi center, Phase 1 (dose escalation) and Phase 2a (dose expansion) study&#xD;
      design to evaluate safety, tolerability, PK, PD and anti-tumor effects of ALRN-6924, alone or&#xD;
      in combination with palbociclib, in patients with advanced solid tumors or lymphomas with&#xD;
      wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt&#xD;
      the interaction between the p53 tumor suppressor protein and its predominant endogenous&#xD;
      inhibitors, murine double minute 2 (MDM2) and murine double minute X (MDMX).&#xD;
&#xD;
      The Phase 1 portion of the study will enroll adults with histologically or cytologically&#xD;
      confirmed malignancies that are metastatic or unresectable and for which standard&#xD;
      treatment(s) are not available or are no longer effective. The Phase 2a portion of the study&#xD;
      consists of separate cohorts that will enroll distinct groups of patients with specific solid&#xD;
      tumors and/or lymphomas to further investigate the clinical safety profile and potential&#xD;
      efficacy of ALRN-6924 alone or in a combination regimen.&#xD;
&#xD;
      Treatment will continue until unacceptable toxicity, patient or physician decision to&#xD;
      discontinue therapy or disease progression that is either symptomatic, rapidly progressive,&#xD;
      requires urgent intervention or is associated with a decline in performance status.&#xD;
&#xD;
      Patients with PTCL have been selected as a group to be further studied in Phase 2a.&#xD;
&#xD;
      Patients with MDM2-amplified or MDM2/CDK4-co-amplified solid tumors have been selected as&#xD;
      another group to be further studied in Phase 2a.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">April 2020</completion_date>
  <primary_completion_date type="Actual">March 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_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</measure>
    <time_frame>From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0</description>
  </primary_outcome>
  <primary_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</measure>
    <time_frame>From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine the maximum tolerated dose (MTD) - Phase 1</measure>
    <time_frame>From the first dose until the end of the first cycle (each cycle is 28 days)</time_frame>
    <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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine Overall Response Rate - Phase 2</measure>
    <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</time_frame>
    <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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas</measure>
    <time_frame>8 weeks</time_frame>
    <description>Peak Plasma Concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas</measure>
    <time_frame>8 weeks</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time of Peak Plasma Concentration (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response</measure>
    <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</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess additional pharmacologic properties, including biomarkers and immunogenicity</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">149</enrollment>
  <condition>Solid Tumor</condition>
  <condition>Lymphoma</condition>
  <condition>Peripheral T-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Dose Regimen A (DR-A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Regimen B (DR-B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Regimen C (DR-C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination with palbociclib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALRN-6924</intervention_name>
    <description>ALRN-6924 will be administered as an IV infusion</description>
    <arm_group_label>Combination with palbociclib</arm_group_label>
    <arm_group_label>Dose Regimen A (DR-A)</arm_group_label>
    <arm_group_label>Dose Regimen B (DR-B)</arm_group_label>
    <arm_group_label>Dose Regimen C (DR-C)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Histologically or cytologically confirmed solid tumor or lymphoma that is not amenable&#xD;
             to standard therapies.&#xD;
&#xD;
          -  Cohort specific biomarkers, including confirmed or anticipated WT TP53 (Phase 1 and&#xD;
             PTCL expansion cohorts) and MDM2-amplification or MDM2/CDK4-co-amplification (solid&#xD;
             tumor expansion cohort)&#xD;
&#xD;
          -  At least one target lesion that is measurable by RECIST 1.1, RANO or IWG 2014, as&#xD;
             appropriate for tumor type&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1&#xD;
&#xD;
          -  Adequate coagulation and hematologic function&#xD;
&#xD;
          -  Adequate hepatic and renal function&#xD;
&#xD;
          -  Sufficient wash out from prior therapies and recovery from all significant acute&#xD;
             toxicities&#xD;
&#xD;
        Key Exclusion Criteria&#xD;
&#xD;
          -  Prior treatment with an MDM2 inhibitor, with protocol specified exceptions&#xD;
&#xD;
          -  Known hypersensitivity to any study drug component&#xD;
&#xD;
          -  Protocol specified cardiovascular risk factors&#xD;
&#xD;
          -  Clinically significant gastrointestinal bleeding within 6 months&#xD;
&#xD;
          -  Clinically significant third-space fluid accumulation&#xD;
&#xD;
          -  Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C&#xD;
&#xD;
          -  HPV positive tumors&#xD;
&#xD;
          -  Second malignancy within two years, with protocol specified exceptions&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>July 13, 2020</last_update_submitted>
  <last_update_submitted_qc>July 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02264613
org study id: ALRN-6924-1-01
nct id: NCT02264613
lead sponsor: 
has dmc: No
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid
      tumors or lymphomas with WT TP53.
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.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
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)
description: Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
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
time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
description: Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
measure: Determine the maximum tolerated dose (MTD) - Phase 1
time frame: From the first dose until the end of the first cycle (each cycle is 28 days)
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
measure: Determine Overall Response Rate - Phase 2
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
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: Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas
time frame: 8 weeks
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
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
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
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
description: The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers
arm group label: Dose Regimen A (DR-A)
arm group type: Experimental
description: Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
arm group label: Dose Regimen B (DR-B)
arm group type: Experimental
description: Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
arm group label: Dose Regimen C (DR-C)
arm group type: Experimental
description: Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle
arm group label: Combination with palbociclib
arm group type: Experimental
description: 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
intervention type: Drug
intervention name: ALRN-6924
description: ALRN-6924 will be administered as an IV infusion
arm group label: Combination with palbociclib
arm group label: Dose Regimen A (DR-A)
arm group label: Dose Regimen B (DR-B)
arm group label: Dose Regimen C (DR-C)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell, Peripheral