Evaluating Emavusertib for Relapsed or Refractory Primary Central Nervous System Lymphoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial is designed to assess the safety, pharmacokinetics, and anti-cancer activity of emavusertib, both as a standalone treatment and in combination with ibrutinib, for adults with relapsed or refractory primary central nervous system lymphoma. The study is divided into four parts, with initial phases focusing on dose escalation and safety evaluation, followed by an assessment of efficacy in patients who have progressed on prior treatments. Participants will receive oral emavusertib at varying doses, depending on their treatment cohort. The trial aims to provide insights into the potential benefits of this combination therapy for a challenging patient population.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Males and females greater than or equal to 18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.

   1. Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion \[≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging \[MRI\] or head computed tomography \[CT\] on imaging within 28 days prior to Cycle 1 Day 1\]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
   2. For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1.

Exclusion Criteria for Part B and Part C

1. Participants with only intraocular PCNSL without brain lesion or CSF involvement, T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS
2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).
3. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.
4. Active malignancy other than PCNSL requiring systemic therapy
5. Previous BTKi treatment (Part C only).
6. History of Grade ≥ 3 rhabdomyolysis without complete recovery
7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
9. Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only).

   Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval
10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)
11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.

Where it's running

• St. Joseph's Hospital and Medical Center
  Phoenix, Arizona, United States Recruiting
• City of Hope
  Duarte, California, United States Recruiting
• Providence St. John's Health Center
  Santa Monica, California, United States Recruiting
• Mayo Clinic
  Jacksonville, Florida, United States Recruiting
• Northwestern Memorial Hospital
  Chicago, Illinois, United States Recruiting
• Dana Farber Cancer Institute
  Boston, Massachusetts, United States Recruiting

Study contacts

• Study coordinator: Ahmed Hamdy, MD
• Email: clinicaltrials@curis.com
• Phone: 617-503-6500

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.