High CR Rates Noted With Zilovertamab Vedotin/R-CHP in DLBCL

Fact checked by" Morgan Bayer
News
Article

Almost a 100% complete response rate was noted with Zilovertamab Vedotin/R-CHP for patients with DLBCL.

Almost a 100% complete response rate was noted with Zilovertamab Vedotin/R-CHP for patients with DLBCL.

Almost a 100% complete response rate was noted with Zilovertamab Vedotin/R-CHP for patients with DLBCL.

Results from the phase 2 WAVELINE-007 (NCT05406401) trial emitted almost a 100% complete response (CR) rate when zilovertamab vedotin to cyclophosphamide, doxorubicin, prednisone, and rituximab (R-CHP) for patients with diffuse large B cell lymphoma (DLBCL), according to a presentation from the 2024 American Society of Hematology Annual Meeting and Exposition.

In the dose escalation study, the objective response rate (ORR) across all doses was 97.2% (95% CI, 85.5%-99.9%), which consisted entirely of CR. At the zilovertamab vedotin recommended phase 2 dose (RP2D) of 1.75 mg/kg every 3 weeks, the ORR was 100% (95% CI, 78.2%-100.0%), which also was entirely comprised of CR. The median duration of response was not yet reached in any group, with a 12-month duration of response of 93.5% across all doses and 91.7% for the RP2D arm.

"Zilovertamab vedotin plus R-CHP demonstrated efficacy and robust responses as front-line treatment for DLBCL with a manageable safety profile," lead investigator Muhit Ozcan, MD, Hematology Department, Ankara University School of Medicine, Cankaya-Ankara, Turkey, said during a presentation of the results. "These results warrant further evaluation of this combination in a larger population."

Zilovertamab vedotin is an antibody-drug conjugate consisting of a ROR1-targeting antibody with an MMAE cytotoxic payload. In general, Ozcan noted, ROR1 is expressed across all lymphoid malignancies and in studies a correlation was not seen between expression levels and efficacy with the agent. As a result, testing for ROR1 was not a prerequisite for the study.

For the study, intravenous doses of zilovertamab vedotin were escalated in 0.25 mg/kg increments between 1.75 mg/kg and 2.25 mg/kg every 3 weeks for no more than 8 cycles. Even though 8 cycles were allowed, most used the more standard 6 cycles, which is common with R-CHOP, Ozcan noted.

Of the 36 patients enrolled, 15 completed treatment at the 1.75 mg/kg dose, 14 of 15 completed treatment at the 2.0 mg/kg dose, and 5 of 6 completed treatment at the 2.25 mg/kg dose. There were 2 patient discontinuations before treatment completion. Both were listed as physician decision. All patients also received R-CHP. The vincristine was omitted from the traditional R-CHOP regimen due to potentially overlapping adverse events (AEs) with the investigational agent, Ozcan said.

The median age was 64.0 years across all 36 enrolled patients. The ECOG performance status across all patients was 0 (42%) and 1 (58%). Bone marrow involvement was noted for 11% of patients and half of patients had Ann Arbor stage IV disease (50%). By NCCN-IPI criteria, 58% of patients were low-intermediate risk with the remainder being high-intermediate risk (33%) and high risk (8%). The DLBCL cell of origin was germinal center B-cell-like for 28% and activated b-cell for 11% with the remainder unknown.

The ORR in the 2.0 mg/kg arm was 93.3% (95% CI, 68.1%-99.8%), which was entirely CRs. The 12-month duration of response in this group was 92.3%. In the 2.25 mg/kg group, the ORR, also entirely CRs, was 100%, and the 12-month duration of response was 100%. Across all doses, every patient experienced more than a 60% reduction in the target lesion size from baseline, with more than a quarter experiencing a 100% reduction.

At the RP2D, there was no dose-limiting toxicity (DLT) with the zilovertamab vedotin combination. At the 2.0 mg/kg dose, there were 2 events, 1 being diarrhea and the other pneumonia. Two patients experienced DLT events at the 2.25 mg/kg dose level, both experienced febrile neutropenia along with hypokalemia in 1.

Treatment-related adverse events (TRAE) were experienced by all patients enrolled in the study. In the RP2D arm, 1 of these events (7%) was deemed serious. Five patients (33%) experienced a grade 3 or 4 TRAE at the RP2D. This increased to nearly all patients in the 2.00 and 2.25 mg/kg arms (73% and 83%, respectively). One patient discontinued treatment in the 2.0 mg/kg arm due to an AE. There were no other discontinuations of zilovertamab vedotin.

A phase 3 study to further examine zilovertamab vedotin is currently being planned under the name waveLINE-010. In this study, the zilovertamab vedotin/R-CHP regimen will be compared with traditional R-CHOP in previously untreated DLBCL. Additionally, further research in the waveLINE-007 study is planned to explore a 1.5 mg/kg dose of zilovertamab vedotin, Ozcan noted.

Reference

Ozcan M, Barca EG, Kim TM, et al. Waveline-007: Dose Escalation and Confirmation, and Efficacy Expansion Trial of Zilovertamab Vedotin in Combination with Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab in Patients with Diffuse Large B Cell Lymphoma. Presented at: ASH 2023 Annual Meeting & Exposition. December 7-10; San Diego, CA. Abstract #578.

Recent Videos
Success with the 177Lu-PSMA-617 radioligand therapy would be transformative for the clear cell renal cell carcinoma treatment landscape.
An ongoing phase 1 trial seeks to prove XmAb819 as an effective treatment and ENPP3 as a plausible target in patients with relapsed or refractory RCC.
“The therapy is designed to prevent both CAR T-cell inactivation and to restore the anti-tumor immunity of the white blood cells that have gotten through the tumor,” said Marasco, MD, PhD.
Ongoing studies aim to combine base immunotherapy regimens with novel agents to potentially improve outcomes among patients with kidney cancer.
Investigators have found a way to reduce liver and biliary toxicity when targeting the molecule CAIX in patients with clear cell renal cell carcinoma.
Neoantigen-targeting vaccines resulted in an absence of recurrence in 9 patients with high-risk kidney cancer, according to David A. Braun, MD, PhD.
The Kidney Cancer Research Consortium may allow collaborators to form more mechanistic and scientifically driven efforts in the field.
Wayne A. Marasco, MD, PhD, stated that by targeting 2 molecules instead of 1, higher levels of tumor cell killing can be achieved in patients with clear cell renal cell carcinoma.
Leading experts in the breast cancer field highlight the use of CDK4/6 inhibitors, antibody-drug conjugates, and other treatment modalities.
Related Content