Lymphoma limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL). Patients were also required to have received at least one prior anti-CD20 based therapeutic regimen, have a life expectancy of greater than 3 months, an Eastern Cooperative Oncology Group Performance status of 2 or lower, and adequate hematological, renal, and hepatic function.

Eligible participants had R/R DLBCL, FL, MZL/MALT, or MCL (WHO 2008 criteria) with 1-6 prior therapies (including anti-CD20); relapsed DLBCL patients required &ge;24-week response post-first-line or &ge;8-week response post-HD-ASCT. Exclusions: CLL/SLL, primary refractory DLBCL (<24-week response), HD-ASCT candidates, active hepatitis, pregnancy, prior anti-CD37 therapy, CNS involvement, cardiac dysfunction, or severe lung disease.

The study evaluates treatment-emergent adverse events (TEAEs) over 38 months, including clinically significant lab abnormalities (hematology, serum chemistry, urinalysis, coagulation), ECG changes, and vital sign deviations. Secondary outcomes include objective response rate (ORR) based on RECIST criteria (CR: disappearance of target lesions; PR: ≥50% tumor reduction) assessed until disease progression or new therapy initiation.

Key pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, t1/2, CL, Vss, Tmax) for Debio 1562 and rituximab were measured across cycles (21-day intervals) up to 37 months. Efficacy endpoints included PFS (time to progression/death), TTR (time to first response), DOR (response duration), and OS (time to death), with PD defined as new lesions, >50% tumor growth, or nodal enlargement >1.5 cm. Anti-drug antibodies (ADA) against Debio 1562 were monitored.

CD37-positive human diffuse large B-cell lymphoma cell line OCI-LY7 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 10, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates IMGN529 was intravenously administered at a dose of 3 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.

CD37-positive human diffuse large B-cell lymphoma cell line WSU-DLCL2 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 8, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates IMGN529 was intravenously administered at a dose of 3 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.

CD37-positive human diffuse large B-cell lymphoma cell line NU-DUL-1 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 14, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates IMGN529 was intravenously administered at a dose of 3 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.

CD37-positive human diffuse large B-cell lymphoma cell line SU-DHL-8 (ATCC) was subcutaneously inoculated at a dose of 5x106 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 16, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates IMGN529 was intravenously administered at a dose of 10 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.