[Phase I part] To investigate the safety, tolerability, and pharmacokinetics of MT-2111 monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). In addition, the dose to be used in the Phase II part will be confirmed.

[Phase II part] To evaluate the efficacy of MT-2111 monotherapy in patients with relapsed/refractory DLBCL. In addition, the safety and pharmacokinetics will be investigated.

Inclusion Criteria:

• Patients who were diagnosed pathologically with DLBCL, NOS, DLBCL transformed from indolent B-cell lymphoma, or high-grade B-cell lymphoma with DLBCL morphology and with MYC and BCL2 and/or BCL6 rearrangements, based on the 2017 WHO classification.
• Patients with relapsed or refractory disease despite 2 or more prior systemic therapies.
• Japanese patients aged ≥ 18 years at the time of informed consent. For Japanese subjects, it should be confirmed that the parents who are related by blood to the subject must be Japanese.
• Patients who have a lesion that can be assessed for staging and evaluated for response according to the Lugano criteria (2014). A lesion that has received radiotherapy as the most recent treatment will be considered as a measurable lesion only when progression has been documented following completion of the radiotherapy.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.

Exclusion Criteria:

• Patients with a pathological diagnosis of Burkitt's lymphoma.

• Patients with bulky disease with the longest dimension of ≥ 10 cm.

• Patients with a history or complication of post-transplant lymphoproliferative disorders.

• Patients with lymphoma with active central nervous system involvement at the time of screening, including leptomeningeal disease.

• Patients complicated with other active malignancies or patients with a history of other malignancies within 3 years before informed consent. However, the following are exceptional:

  • Non-melanoma skin cancer
  • Non-metastatic prostate cancer
  • Cervical carcinoma in situ
  • Ductal carcinoma in situ or lobular carcinoma in situ

• Patients with clinically significant third space fluid accumulation (e.g., ascites requiring drainage or pleural effusion requiring drainage or associated with shortness of breath).

• Patients who underwent autologous hematopoietic stem cell transplantation (AHSCT) within 30 days prior to the start of study drug administration (Cycle 1 Day 1).

• For the Phase I part, patients with prior allogeneic stem cell transplantation (Allo-HSCT) before the start of study drug administration (Cycle 1 Day 1). For the Phase II part, patients undergoing Allo-HSCT within 60 days prior to the start of study drug administration (Cycle 1 Day 1).

• Patients who had a positive HIV antigen-antibody test or HIV antibody test.

• Patients positive for HBs antigen, HBc antibody, or HBs antibody. However, patients who meet any of the following are eligible:

  • The patient's HBs antibody positivity is clearly due to vaccination.
  • Patients who are positive for HBs antibody and/or HBc antibody with HBV-DNA not detected and agree to undergo HBV-DNA tests once a month from the start of study drug administration to at least 12 months after the completion of study drug administration.

• Patients positive for HCV antibody. However, patients with negative HCV-RNA are eligible.

• Patients who received anticancer therapy during the following periods prior to the start of study drug administration (Cycle 1 Day 1).

  • Cytotoxic chemotherapy: within 14 days.
  • Antibody therapy: within 5 half-lives or 14 days, whichever is longer (including monoclonal antibody preparations, radioimmunoconjugates, or antibody-drug conjugates). Within 14 days for rituximab, anti-CD3/CD20 bispecific antibody.
  • Radiotherapy: within 14 days
  • CAR-T therapy: within 100 days
  • Other anticancer therapy: within 14 days

• Patients who received treatment with any other investigational product within 14 days prior to the start of study drug administration (Cycle 1 Day 1). However, for the Phase I part, patients who received any other investigational product within 14 days or 5 half-lives, whichever is longer, before the start of study drug administration (Cycle 1 Day 1).

When requested by a qualified researcher in the field of science or medicine, Tanabe Pharma Corporation will share clinical trial data that was collected from individual patients in a clinical trial with that researcher after a review committee of experts determines that such sharing is appropriate.

Access Criteria: Please refer to the following link for conditions and limitations for sharing data.

URL: https://www.tanabe-pharma.com/en/develop/protocol.html