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Celyad Oncology’s CAR-T Phase Ib Trial put on FDA Clinical Hold in Latest Setback

Anna Osborne
9 March 2022
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Celyad Oncology has announced that the FDA has placed the Phase Ib trial of their CAR-T product for refractory metastatic colorectal cancer – CYAD-101-002 – under clinical hold, following two clinical fatalities.

The clinical-stage biotechnology company Celyad, who focus on the development of CAR-T therapies for cancer, launched the Phase Ib trial of their TCR Inhibitory Molecule (TIM)-based allogenic NKG2D CAR-T cell therapy in collaboration with the biopharmaceutical company Merck, in December 2021.

In February 2021 Celyad made the decision to voluntarily pause the trial themselves. With patient safety at the forefront, and reports of two patient fatalities, patient dosing and enrolment were halted, pending investigation.

The findings reported that the two fatalities presented with similar pulmonary findings. These, and additional events experienced by other patients on the study are being investigated by Celyad.

Subsequently, the FDA have now announced to launch their own investigation due to “insufficient information to assess risk to study subjects”.

The Phase Ib EYNOTE-B79 trial combined the concurrent administration of CYAD-101 with FOLFOX chemotherapy, followed by Merck’s anti-PD-1 therapy, KEYTRUDA, in the first clinical trial to measure the potential complementary pathway of allogenic CAR-T with an anti-PD-1 in solid tumours. In particular, the significantly un-met medical needs of metastatic colorectal cancer.

However, less than two months into the phase Ib trial and tragically two fatalities have taken place, prompting the FDA clinical hold.

“We are working diligently to better understand these events…our primary commitment is to maintain patient safety, which is why we decided to place the trial on hold while we investigate these events,” comments Filippo Petti CEO of Celyad Oncology.

This news comes following a recent stream of FDA clinical holds to hit advanced therapies trials.

Legend Biotech last month reported their Phase I clinical trial for LB1901, a CAR-T for relapsed or refractory T-cell lymphoma, had been put on clinical hold by the FDA. The decision was made after thye first patient to be dosed experienced low CD4+ T-cell counts.

In December 2021 bluebird bio announced the FDA had placed their clinical program for lovo-cel – a gene therapy for patients under 18 with sickle cell disease – on partial clinical hold. This followed an on-going investigation into a patient with persistent anaemia 18-months’ after receiving lovo-cel treatment. Under standard procedure bluebird bio have received written questions from the agency for their investigation.

In some more positive news Allogene Theraputics announced in January the removal of their FDA clinical hold on all five of the companies allogenic CAR-T products for cancer treatments, after a 3 month long holding period. The FDA’s decision to pause all AlloCAR-T trials was in response to the report of a chromosome abnormality detected in a patient administrated with ALLO-501A. The FDA concluded there was no clinical significance to this detection, and Allogene’s clinical trials have been allowed to resume.

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer at Allogene, sheds light on the FDA clinical hold process, “We are thankful for the partnership between our teams at Allogene, our clinical trial investigators who remain steadfast in their support of our investigational therapies, and the FDA which expeditiously completed its review of our Complete Response Letter.”

Sources: Press Release from Celyad Oncology, Legend Biotech, bluebird bio, Allogene Theraputics