Analysts called the data “very competitive” but raised questions about safety. Merck gained ownership of the ADC when it acquired VelosBio in November 2020 for $2.75 billion.
Merck on Sunday unveiled initial data from the Phase II waveLINE-007 study, demonstrating that its investigational antibody-drug conjufate zilovertamab vedotin achieved a 100% complete response rate when used as part of a treatment regimen in patients with diffuse large B cell lymphoma.
The pharma presented these findings at the ongoing 66th annual meeting of the American Society of Hematology (ASH 2024), being held in San Diego.
In a note over the weekend, BMO Capital Markets analysts called data for Merck’s ADC “very competitive,” however noting that “safety remains more of a question” moving forward.
In the study, all 15 patients treated with 1.75 mg/kg of zilovertamab vedotin, in combination with the anti-cancer regimen R-CHP—cyclophosphamide, doxorubicin, prednisone and rituximab—reached complete response, as assessed using a PET scan and a CT or MRI scan.
At a higher dose level of 2 mg/kg, complete response rate (CRR) dipped slightly to 93.3%, before going back up to 100% in the six patients who were dosed at 2.25 mg/kg. The overall CRR at the end of the treatment period was 97.2%. At the time of the readout, median duration of response has not yet been reached for all patients.
As for safety, waveLINE-007 documented grade 3 to 4 treatment-related adverse events in 58% of patients, the most common of which were nausea, neutropenia, anemia and diarrhea. Serious treatment-related toxicities arose in 11%, most of whom were given the highest zilovertamab vedotin dose. None of the patients in the 1.75 mg/kg arm dropped out of the study, while one participant in the highest dose bracket had to discontinue, as deemed appropriate by their physician.
Based on these findings, Merck will take the 1.75 mg/kg dose of zilovertamab vedotin forward into Phase III testing.
Zilovertamab vedotin targets the ROR1 transmembrane protein, which is highly expressed in blood cancer cells. The ADC carries a monomethyl auristatin E payload, which when released inside the cell disrupts microtubules, prevents cell division and ultimately triggers cell death.
Merck gained ownership of zilovertamab vedotin in November 2020, when it bought San Diego biotech VelosBio for $2.75 billion. At the time, the ADC was still in early-to-mid-stage development, but Merck has since expanded the development program for zilovertamab vedotin. In addition to the , including the waveLINE-007, the company has two other ongoing trials in the same indication, diffuse large B cell lymphoma (DLBCL): the Phase II/III waveLINE-003 study for relapsed or refractory DLBCL and the Phase III waveLINE-010 trial in treatment-naive DLBCL patients.
