HEME-25: Open-Label Feasibility Study of Elranatamab Utilized in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV

Inclusion Criteria:

* Age ≥ 18 years at time of consent
* ECOG performance status (PS) 0 or 1
* Histologically and immunophenotypically confirmed PBL
* Ann Arbor stage at initial diagnosis: stage I with lactate dehydrogenase (LDH) \> upper limit of normal (ULN) and/or bulky disease \>7.5 cm or stage II-IV
* Received definitive front-line therapy for PBL with end-of-treatment PR or CR
* Adequate bone marrow function with recovery from prior therapy, defined as:

  * ANC ≥ 500 cells/mcL
  * Platelet count ≥ 50,000 cells/mcL
* Availability of archival tumor tissue (block or unstained slides) for mandatory central pathology review and correlative BCMA testing. Central pathology review and BCMA testing may be completed after enrollment.
* Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. If a subject is unable to consent, a LAR may provide consent on their behalf.
* As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study
* If capable of becoming pregnant: Negative serum or urine pregnancy test
* If HIV-positive:

  * Receiving effective combined antiretroviral therapy
  * CD4+ T-cell count ≥ 50 cells/mcL within 4 weeks before enrollment

Exclusion Criteria:

Key inclusion criteria:

* Age ≥ 18 years at time of consent
* ECOG performance status (PS) 0 or 1
* Histologically and immunophenotypically confirmed PBL
* Ann Arbor stage at initial diagnosis: stage I with lactate dehydrogenase (LDH) \> upper limit of normal (ULN) and/or bulky disease \>7.5 cm or stage II-IV
* Received definitive front-line therapy for PBL with end-of-treatment PR or CR
* Adequate bone marrow function with recovery from prior therapy, defined as:

  * ANC ≥ 500 cells/mcL
  * Platelet count ≥ 50,000 cells/mcL
* Availability of archival tumor tissue (block or unstained slides) for mandatory central pathology review and correlative BCMA testing. Central pathology review and BCMA testing may be completed after enrollment.
* Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. If a subject is unable to consent, a LAR may provide consent on their behalf.
* As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study
* If capable of becoming pregnant: Negative serum or urine pregnancy test
* If HIV-positive:

  * Receiving effective combined antiretroviral therapy
  * CD4+ T-cell count ≥ 50 cells/mcL within 4 weeks before enrollment

Key exclusion criteria:

* Prior BCMA bispecific therapy
* Stable or progressive disease following front-line therapy as determined by the investigator
* Receiving any other investigational agents
* Expected survival \< 2 months
* Known or suspected PBL involvement of the parenchymal brain or spinal cord at diagnosis. Asymptomatic leptomeningeal disease only will be allowed.
* Uncontrolled intercurrent illness, including but not limited to uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Concurrent malignancy requiring active therapy within the last 3 years, except for the following:

  * Basal cell carcinoma limited to the skin
  * Squamous cell carcinoma limited to the skin
  * Carcinoma in situ of the cervix or breast
  * Adequately treated lentigo malignant melanoma
  * Localized prostate cancer
  * Active therapy consists of adjuvant or maintenance therapy to reduce the risk of recurrence of a malignancy that was previously treated with curative intent and with no evidence of active disease within 2 years prior to screening
* Pregnant or nursing
* PWH with a history of AIDS-defining opportunistic infection within the past year
* Receipt of a live vaccine within 28 days prior to the first dose of study treatment