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ADC for Non-Hodgkin Lymphoma

Published: 2018-10-16 |

Author: Bryant Furlow |

Source: Cancer Therapy Advisor

The Leukemia & Lymphoma Society (LLS) and Sutro Biopharma have partnered for a phase 1 clinical study of the firm's first-in-class, CD74-targeting antibody-drug conjugates (ADC) STRO-001 against refractory and/or relapsed non-Hodgkin lymphoma. CD74 is highly expressed on the surface of malignant B cells. Were it to prove safe and effective, STRO-001 could represent a much-needed treatment for patients whose current options are limited.

ADC's use engineered antibodies to target cancer cell surface proteins for delivery of a chemotherapy warhead, maximizing doses delivered to tumors while sparing surrounding tissues. Each ADC molecule contains a monoclonal antibody, a cytotoxic payload, and a covalent linker attaching these units.

Early ADC development was challenging, beset by imprecise antibody-drug conjugation, unreliable targeting, off-target efforts, and disappointing outcomes during clinical testing. Gemtuzumab ozogamicin, a CD33-directed ADC, was approved for teating acute myeloid leukemia (AML) until 2010, when it was voluntarily taken off the market following clinical trial evdence of increased patient mortality and the determination that there was no benefit from treatment with drug compared with conventional therapies. In 2017, the product returned to the market with a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population.

The CD30-targeting ADC brentuximab vedotin is a treatment for relapsed of refactory Hodgkin lymphoma, systemic anaplastic large cell lymphoma, relapsed primary cutaneous anaplastic large cell lymphoma, or CD30-expressing mycosis fungoides. The CD-22 targeting ADC inotuzumab ozogamicin is used in the management of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

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