Clinical Trials /

ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas

NCT02264613

Description:

This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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 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

DrugSynonymsArms
ALRN-6924Dose Regimen A (DR-A)

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 dose escalation (DEP) and dose expansion (EXP) study designed to
      evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor
      effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with wild-type (WT)
      TP53. ALRN-6924 is a stapled peptide designed to disrupt integration between the p53 tumor
      suppression protein and inhibition by murine double minute 2 (MDM2) and murine double minute
      X (MDMX).

      The DEP 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 can be enrolled.The EXP
      portion of the study 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 at the MTD or OBD. PTCL has been selected as one of the EXP groups to be further
      studied.

      Treatment of patients in the DEP and EXP phases will continue in the study until
      documentation of disease progression, unacceptable toxicity, or patient or physician decision
      to discontinue study participation is made.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Regimen A (DR-A)ExperimentalFixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
  • ALRN-6924
Dose Regimen B (DR-B)ExperimentalFixed dose of ALRN-6924 per cohort, administered IV, Days 1, 4, 8 and 11 every 21 days
  • ALRN-6924

Eligibility Criteria

        Inclusion Criteria

          -  Male or female patients age 18 years and older, inclusive, at the time of informed
             consent

          -  Histologically- or cytologically-confirmed malignancy that is metastatic or
             unresectable and for which standard measures do not exist or are no longer effective
             (DEP) or a histologically confirmed diagnosis of PTCL based on pathology review at the
             local institution, using the most recent edition of the WHO Classification, relapsed
             or refractory disease after at least one prior systemic anticancer regimen (EXP in
             PTCL)

          -  WT TP53 status

          -  At least one target lesion that is measurable by RECIST 1.1 for solid tumors, or IWG
             2014 for lymphoma

          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1

          -  Adequate hematologic function

          -  Adequate hepatic function

          -  Acceptable coagulation profile

          -  Recovery from significant toxicities from previous therapies and sufficient time since
             last dose of previous therapy

        Exclusion Criteria:

          -  Previous treatment with investigational agents that inhibit MDM2 or MDMX activity
             (some MDM2-treated patients may be eligible)

          -  Known hypersensitivity to any study drug component

          -  Known and untreated brain metastases. Patients with primary CNS (central nervous
             system) malignancies are excluded.

          -  History of coagulopathy, platelet disorder or history of non-drug induced
             thrombocytopenia

          -  History of pulmonary embolism within 6 months prior to the first dose of ALRN-6924 or
             untreated DVT (deep vein thrombosis)

          -  Required concurrent use of anti-coagulants or anti-platelet medication, with the
             exception of aspirin doses ≤81 mg/day, low-dose SC heparin or SC low-molecular-weight
             heparin for DVT prophylaxis, or heparin flushes to maintain IV catheter patency

          -  Patients with pre-existing history of or known cardiovascular risk

          -  Clinically significant gastrointestinal bleeding within 6 months prior to the first
             dose of ALRN-6924

          -  Clinically significant third-space fluid accumulation

          -  Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C

          -  Patients with cancers likely to be Human Papilloma Virus (HPV)-positive such as
             cervical cancers, oropharyngeal cancers or anal cancers must undergo additional
             screening to determine eligibility

          -  Known history of another primary malignancy that has not been in remission for ≥2
             years

          -  Required use of medications predominantly cleared by hepatobiliary transporters within
             48 hours of study drug infusion
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine maximum tolerated dose (MTD) - DEP Phase
Time Frame:From first dose up to 30 days after last dose
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics of ALRN-6924: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame:2 months
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924: Maximum plasma concentration (Cmax)
Time Frame:2 months
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
Time Frame:2 months
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924: Half-life (t1/2)
Time Frame:2 months
Safety Issue:
Description:
Measure:RECIST (Response Evaluation Criteria in Solid Tumors): primary tumor
Time Frame:2 months
Safety Issue:
Description:Imaging of primary solid tumor site
Measure:International Working Group response criteria: primary tumor (lymphoma patients)
Time Frame:2 months
Safety Issue:
Description:The International Working Group criteria is used to define and measure response in lymphoma patients

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aileron Therapeutics

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