The ADC zilovertamab vedotin plus Rituxan and chemo confirmed an ORR of 56.3% in relapsed/refractory DLBCL: © inventory.adobe.com.
Amongst sufferers with with relapsed or refractory diffuse massive B-cell lymphoma (DLBCL), zilovertamab vedotin, a ROR1-targeted antibody-drug conjugate, plus Rituxan (rituximab) and gemcitabine-oxaliplatin (R-GemOx) elicited an goal response charge of 56.3%, in keeping with findings from the section 2/3 waveLINE-003 examine which have been shared on the 2025 ASCO Annual Assembly.
On the suggest section 2 dose of 1.75 milligrams per kilogram (mg/kg) for zilovertamab vedotin plus normal R-GemOx, the entire response charge was 50% within the examine. After a median of 9.9 months of follow-up, the median length of response was 8.7 months, with 28.6% of sufferers persevering with to reply at 9 months. The median general survival was not but reached, with a 12-month estimated general survival charge of 68.9% on the RP2D.
“This mixture had a manageable security profile, and the target and full response charge of 56% and 50% of the zilovertamab vedotin plus R-GemOx mixture on the really useful section 2 dose counsel improved exercise in relapsed/refractory DLBCL,” stated principal investigator Dr. Philippe Armand, from Dana-Farber Most cancers Institute. “The examine is at the moment enrolling the section 3 portion.”
The section 2 portion of the examine enrolled 40 contributors with relapsed/refractory DLBCL. R-GemOx was administered at normal doses in every group, with zilovertamab escalated throughout three dose ranges. There have been 17 sufferers who obtained 1.5 mg/kg, 16 receiving 1.75 mg/kg, and 7 who obtained 2.0 mg/kg. Throughout all teams, the median variety of prior therapies was two, with two particularly having obtained the CD79b-directed Polivy (polatuzumab vedotin). Armand famous this agent particularly, because it carries the identical cytotoxic payload as zilovertamab vedotin; nevertheless, knowledge weren’t proven for this subgroup through the presentation.
Throughout all sufferers enrolled, the median age was 66.5 years, with 55% being 65 years or older. ECOG efficiency standing was zero (43%), one (48%), and two (10%) and practically half of sufferers had Ann Arbor stage IV illness (53%). The DLBCL cell of origin was mostly GCB (45%).
On the 1.5 mg/kg dose, the general response charge was 26.7% with a whole response charge of 20.0%. The median length of response on this group was 14.4 months, with a 9-month length of response charge of 100%. The median general survival was 11.5 months on this group, with a 12-month general survival charge of 40.8%. The median follow-up for this dose stage was 18.1 months.
Within the 2.0 mg/kg group, the general response charge was 57.1%, with a whole response charge of 42.9%. The median length of response on this group was not but reached. The median general survival on this group was 7.4 months, with a 12-month general survival charge that was not but reached. The median follow-up on this cohort was 9.3 months.
“The apparent caveat listed below are the few sufferers and nonetheless restricted length of comply with up. So, the estimates should not very secure,” Armand cautioned relating to the response length knowledge.
There was a complete of seven dose limiting toxicities noticed throughout the three dose ranges. On the 2.0-mg/kg dose, there have been 4, in contrast with one within the 1.5-mg/kg group and two on the really useful section 2 dose group. Within the 2.0-mg/kg dose stage, there was one treatment-related loss of life from sepsis.
Different dose limiting toxicities on this group included grade 3 diarrhea, grade 4 neutrophil rely lower, grade 4 thrombocytopenia, grade 3 febrile neutropenia, and grade 4 neutrophil rely lower. To deal with these negative effects, halfway by way of the trial the protocol was tailored to included necessary prophylaxis with G-CSF. Within the really useful section 2 dose arm, the dose limiting toxicities have been grade 3 alanine aminotransferase enhance and intestinal obstruction.
This mixture had a manageable security profile, and the target and full response charge of 56% and 50% of the zilovertamab vedotin plus R-GemOx mixture on the really useful section 2 dose counsel improved exercise in relapsed/refractory DLBCL.
Zilovertamab vedotin-related negative effects of grade 3 (extreme)/4 (life threatening) in severity have been skilled by 63% of sufferers within the really useful section 2 dose group. This in contrast with 86% of these within the largest dose and for 53% of these within the lowest dose. Two sufferers discontinued the drug within the highest dose group, associated to sepsis and respiratory fatigue. There have been no discontinuations on the different dose ranges. Critical drug-related negative effects have been skilled by 24% of these within the low dose group, by 31% on the really useful section 2 dose group, and for 57% of these on the 2.0 mg/kg dose.
A number of research proceed to discover zilovertamab vedotin for sufferers with DLBCL, together with the section 3 portion of the waveLINE-003 examine. Armand additionally drew consideration to research taking a look at zilovertamab vedotin as a first-line therapy for DLBCL together with chemotherapy in contrast with chemo alone. Moreover, waveLINE-011 is investigating zilovertamab vedotin with chemo as a first-line remedy for the GCB subtype of DLBCL in contrast with Polivy plus chemo.
Reference:
“WaveLINE-003: Part 2/3 trial of zilovertamab vedotin plus normal of care in relapsed/refractory diffuse massive B-cell lymphoma” by Dr. Philippe Armand, et al., American Society of Scientific Oncology Annual Assembly.
