Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas

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 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.

Eligibility: 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

Relevance to patient case: not relevant