A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL

Phase 1

Recruiting

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: MT-2111

• Registration Number: NCT05658562
• Lead Sponsor: Mitsubishi Tanabe Pharma Corporation

Brief Summary

\[Phase I part\] 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-12-13
• Study First Posted: 2022-12-20
• Study Start: 2023-01-30
• Status Verified: 2023-12
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-07
• Primary Completion: 2025-12
• Study Completion: 2028-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 49

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.

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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.
  • 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MT-2111 dosing regimen	MT-2111	-

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) by independent central review	From the date of first dose of study treatment until all participants completed treatment period or discontinued treatment (Up to 12 months)

Secondary Outcome Measures

Name	Time	Method
Duration of response (DOR)	The time from the date of first observation of complete response (CR) or partial response (PR) until progressive disease (PD) or death in patients with CR or PR observed (Up to 48 months)
Progression-free survival (PFS)	The time from the date of first dose until PD or death (Up to 48 months)
Complete response rate (CRR)	From the date of first dose of study treatment until all participants completed treatment period or discontinued treatment (Up to 12 months)
Overall survival (OS)	The time from the date of first dose until death regardless of the occurrence of intercurrent event (Up to 48 months)
Relapse-free survival (RFS)	The time from the date of first observation of CR until PD or death in patients with CR observed (Up to 48 months)
Adverse events and adverse drug reactions	From the start of premedication until 15 weeks after the last dose of the study drug or until the start of new anticancer therapy, whichever comes first.
Eastern Cooperative Oncology Group (ECOG) Performance Status	Screening to end of treatment (up to 30 days after the last dose) or data cut off	ECOG (Eastern Cooperative Oncology Group) Performance Status is scored on a 6-point scale where higher scores indicate a worse outcome.
Body weight	Screening to end of treatment (up to 30 days after the last dose) or data cut off
12-lead electrocardiogram (heart rate)	Screening to end of treatment (up to 30 days after the last dose) or data cut off
12-lead electrocardiogram [RR, PR, QRS, QT (QTcF)]	Screening to end of treatment (up to 30 days after the last dose) or data cut off
12-lead electrocardiogram (presence or absence of abnormal findings)	Screening to end of treatment (up to 30 days after the last dose) or data cut off
Serum drug concentration	Please refer to the description above	\[Phase 1 part\] Cycle 1 \[each cycle is 3 weeks (21 days) in duration\]: Day 1, 2, 5, 8 and 15, Cycle 2: Day 1, 2, 8 and 15, Cycle 3: Day 1 and 8, odd number Cycle: Day 1,end of treatment (EOT)\*, and 15 weeks after EOT\* \[Phase 2 part\] Cycle 1 and 2: Day 1, 8 and 15, odd number Cycle : Day 1, EOT\*, and15 weeks after EOT\*; \*: After the decision to discontinue treatment with study drug and prior to the start of any new anticancer therapy, the scheduled evaluations will be performed preferably 30 days after the last dose of study drug.; One cycle is 3 weeks (21 days) in duration.; \*: After the decision to discontinue treatment with study drug and prior to the start of any new anticancer therapy, the scheduled evaluations will be performed preferably 30 days after the last dose of study drug.
Anti-drug antibodies (including neutralizing antibodies)	Please refer to the description above.	\[Phase 1 part\] Cycle 1 \[each cycle is 3 weeks (21 days) in duration\]: Day 1 and 15, Cycle 2: Day 1, odd number Cycle: Day 1, end of treatment (EOT)\*, and 15 weeks after EOT\* \[Phase 2 part\] Cycle 1: Day 1 and 15, Cycle 2: Day 1, odd number Cycle : Day 1, EOT\*, and 15 weeks after EOT\*; \*: After the decision to discontinue treatment with study drug and prior to the start of any new anticancer therapy, the scheduled evaluations will be performed preferably 30 days after the last dose of study drug.

Trial Locations

Locations (19)

Osaka Saiseikai Nakatsu Hospital; 🇯🇵 Osaka-shi, Osaka, Japan

Nagoya Medical Center; 🇯🇵 Nagoya-shi, Aichi, Japan

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital; 🇯🇵 Nagoya-shi, Aichi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa-shi, Chiba, Japan

Kyushu Cancer Center; 🇯🇵 Fukuoka-shi, Fukuoka, Japan

Aso Iizuka Hospital; 🇯🇵 Iizuka-shi, Fukuoka, Japan

Gunma Prefectural Cancer Center; 🇯🇵 Ota-shi, Gunma, Japan

Hokkaido Cancer Center; 🇯🇵 Sapporo-shi, Hokkaido, Japan

Japanese Red Cross Society Himeji Hospital; 🇯🇵 Himeji-shi, Hyogo, Japan

University Hospital, Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto-shi, Kyoto, Japan

Tohoku University Hospital; 🇯🇵 Sendai-shi, Miyagi, Japan

Shinshu University Hospital; 🇯🇵 Matsumoto-shi, Nagano, Japan

Japanese Red Cross Nagasaki Genbaku Hospital; 🇯🇵 Nagasaki-shi, Nagasaki, Japan

Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai; 🇯🇵 Osaka-shi, Osaka, Japan

Shimane University Hospital; 🇯🇵 Izumo-shi, Shimane, Japan

Tokyo Metropolitan Komagome Hospital; 🇯🇵 Bunkyo-ku, Tokyo, Japan

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Tokyo, Japan

Cancer Institute Hospital of JFCR; 🇯🇵 Koto-ku, Tokyo, Japan

Yamagata University Hospital; 🇯🇵 Yamagata-shi, Yamagata, Japan