AbbVie halts trial of Stemcentrx-sourced ADC for cancer

AbbVie says it remains committed to Stemcentrx platform. (AbbVie)

AbbVie has terminated an early-stage trial of an antibody-drug conjugate (ADC) for solid tumors, one of the candidates acquired as part of its $9.8 billion takeover of Stemcentrx in 2016.

It’s no surprise when phase 1 trials sometimes don’t go as expected but, other than pointing that out, AbbVie declined to give much in the way of additional information to FierceBiotech's initial inquiries on the fate of SC-007.

A spokesman said the study of SC-007 “was a very early stage phase 1 trial with seven patients enrolled, and for which there was a benefit/risk profile imbalance observed,” but did not indicate the nature of the side effects or whether the program was still active.

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He did add however that “we remain committed to oncology research and to the drug discovery platform at Stemcentrix, which we believe has promising and active trials across a broad range of malignancies.”

The phase 1 trial of SC-007 was carried out in subjects with colorectal or gastric cancer and got underway last September. The protocol indicates that the ADC—whose target has not been disclosed—was to be tested using various doses and dose regimens, with the primary outcome measure the number of patients with dose-limiting toxicities.

ADCs take the form of an antibody, linker and drug—generally a toxin—and are designed to deliver a cell-killing payload to malignant tissues while limiting exposure to healthy tissues. Despite hundreds of clinical trials, only a handful have been made available to patients, notably Pfizer’s recently-reintroduced Mylotarg for acute myeloid leukemia, Seattle Genetics/Takeda’s Hodgkin lymphoma therapy Adcetris and Roche’s Kadcyla for breast cancer.

The reason so few make it to market is because ADCs are complex drugs with numerous potential pitfalls that can impact safety, including the selectivity of the targeting antibody, the stability of the ADC in the body and the efficiency with which the cytotoxic payload is taken up into cells, which can lead to off-target side effects.

Just last week, ADC Therapeutics abandoned one of its ADCs, HER2-targeting drug ADCT-502, after it became clear in a phase 1 trial that it would not be able to take the dose high enough to have a therapeutic effects without tolerability issues. That seems to have been be a relatively minor setback for the company’s ADC program, however, as it said six other ADCs will be in the clinic in early 2019, including some using new technology designed to improve the risk:benefit ratio.

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