1 July 2022 - - The first patient has been dosed in LOTIS-7, a Phase 1b clinical trial evaluating Zylonta in combination with other anti-cancer agents in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, Switzerland-based ADC Therapeutics SA (NYSE: ADCT) said.

The first arm of the LOTIS-7 open-label, multi-center, multi-arm Phase 1b trial will evaluate the safety and activity of Zylonta in combination with polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma.

The trial will include multiple arms in two parts a dose escalation part and a dose expansion part.

Zylonta is also being evaluated in the LOTIS clinical trial program as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

Zylonta is a CD19-directed antibody drug conjugate. Once bound to a CD19-expressing cell, Zylonta is internalized by the cell, where enzymes release a pyrrolobenzodiazepine payload.

The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms.

This ultimately results in cell cycle arrest and tumor cell death.

The US Food and Drug Administration has approved Zylonta (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory 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.

The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with Zylonta.

This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Zylonta is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

ADC Therapeutics (NYSE: ADCT) is a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates.

The company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.

ADC Therapeutics' CD19-directed ADC Zylonta (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large b-cell lymphoma after two or more lines of systemic therapy.

Zylonta is also in development in combination with other agents. Cami (camidanlumab tesirine) is being evaluated in a pivotal Phase 2 trial for relapsed or refractory Hodgkin lymphoma and in a Phase 1b clinical trial for various advanced solid tumors.

In addition to Zylonta and Cami, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.

ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London, the San Francisco Bay Area and New Jersey.