On the 17th International Conference on Malignant Lymphoma (ICML), Dr. Alexander Fosså from Oslo University Hospital presented the results of the Zilovertamab vedotin (MK-2140) treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), a Phase II open-label, waveLINE-004 study. Oncology Frontier interviewed Dr. Fosså at the conference.
Oncology Frontier : Due to its high heterogeneity, DLBCL has several subtypes, each with varying prognosis and treatment responses. What is the current treatment status for DLBCL?
Dr. Fosså : For R/R DLBCL, we have gained deep molecular insights into its subtypes, yet no suitable therapeutic targets have emerged. Our current research primarily focuses on CAR-T therapy and bi-specific antibodies. Still, many patients are either not suitable candidates for this treatment or don’t respond to it. Therefore, besides the existing targets in use, we’re exploring other potential ones, such as the ROR1 antigen on the surface of hematological malignancies.
Oncology Frontier : Your team presented the waveLINE-004 study at this conference. Can you provide a detailed overview?
Dr. Fosså : Beyond the targets addressed by CAR-T cells and bi-specific antibodies, ROR1 has emerged as an intriguing find. It’s a surface antigen expressed in most DLBCL patients and is an onco-fetal protein not found in any other normal adult tissues. This uniqueness has made the ROR1 antibody-drug conjugate (ADC) developed by Merck a point of keen interest. We initiated a typical Phase II study for patients unsuitable for, or unresponsive to, autologous transplantation and CAR-T therapies. It’s still in the early stages, and at this conference, we’re sharing data from the first 40 patients.
Oncology Frontier : ROR1 has demonstrated potent anti-tumor activity and controllable safety in R/R DLBCL patients, marking it as an ideal target for anti-tumor drugs. Can you share your views on ROR1’s prospects in hematological oncology?
Dr. Fosså : ROR1 is indeed a promising target. It’s not the typical target addressed by CAR-T cells or specific antibodies. Being a completely tumor-specific target, ROR1 is expressed in DLBCL and, interestingly, in mantle cell lymphomas. This suggests its potential as an alternative or complement to B-cell specific markers. Furthermore, it’s worth exploring if ROR1 plays a role in other lymphomas, such as T-cell lymphomas. Thus, it presents prospects in hemato-oncology that other targets don’t.
TAG: ICML 2023, Interview, Hematological Malignancy, DLBCL
