ADC Therapeutics Plan to Discontinue Phase 2 LOTIS-9 Trial of Zynlonta After Patient Deaths

Rare Daily Staff

ADC Therapeutics said it plans to discontinue the phase 2 LOTIS-9 clinical trial of Zynlonta and rituximab in unfit or frail patients with previously untreated diffuse large B-cell lymphoma, a rare blood cancer.

The decision followed the U.S. Food and Drug Administration move to place a partial clinical hold on the trial for new patient enrollment. The FDA, however, allowed patients already on therapy who are deriving clinical benefit to remain on therapy after being reconsented.

Earlier this month ADC voluntarily paused enrollment in the trial to investigate the death of seven patients in the study and five additional treatment-emergent adverse events. All of the cases involved respiratory-related problems. The company noted at the time that all 12 patients in the LOTIS-9 study would not have qualified for its phase 3 LOTIS-5 trial of Zynlonta in combination with rituximab.

“Given the challenges of defining the addressable segment of the difficult-to-treat unfit or frail DLBCL patient population, including many patients with significant active underlying co-morbidities, the benefit-risk profile does not support continuation of the LOTIS-9 trial,” the company said.

Following treatment of any reconsenting patients, the company said it will conduct the necessary steps to conclude the trial and does not plan to continue studying this regimen in the unfit or frail previously untreated diffuse large B-cell lymphoma patient population.

Zynlonta is a CD19-directed antibody drug conjugate. Once bound to a CD19-expressing cell, Zynlonta is internalized by the cell, where enzymes release a toxic payload. The potent payload binds to DNA causes cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency have approved Zynlonta for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. Both the FDA and European Commission granted orphan drug designation to Zynlonta.