Celyad announced that it is voluntarily pausing a clinical trial it’s conducting with Merck after reports of two patient deaths.
Celyad announced that it is voluntarily pausing a clinical trial it’s conducting with Merck after reports of two patient deaths.
Celyad is conducting the CYAD-101-002 (KEYNOTE-B79) Phase Ib trial of CYAD-101, administered simultaneously with FOLFOX chemotherapy, followed by Merck’s anti-PD-1 checkpoint inhibitor Keytruda (pembrolizumab) in patients with refractory metastatic colorectal cancer. CYAD-101 is a TCR Inhibitor Molecule (TIM)-based allogeneic NKG2D CAR T therapy.
Celyad was informed of two deaths with similar pulmonary symptoms. As a result, the company chose to pause the dosing and enrollment of patients in the study to investigate.
“Our primary commitment is to maintain patient safety, which is why we decided to place the trial on hold while we investigate these events,” said Filippo Petti, Celyad’s CEO. “We are working diligently to better understand these events. In twenty-five patients previously treated with CYAD-101 in the alloSHRINK Phase I trial, which evaluated the TIM-based investigational candidate for the treatment of advanced mCRC, no dose-limiting toxicities were reported. Lastly, we anticipate no impact on our shRNA-based candidates, including CYAD-211 currently under investigation for the treatment of multiple myeloma.”
Celyad’s other ongoing studies include the IMMUNICY-1 Phase I trial of CYAD-211, its allogeneic shRNA-based anti-BCMA CAR T for candidates in relapsed or refractory multiple myeloma. Data has demonstrated evidence of clinical activity with good tolerability and no evidence of Graft versus Host Disease (GvHD).
In 2021, the company also presented clinical data from the Phase I CYCLE-1 trial of CYAD-02, its next-generation autologous NKG2D receptor CAR T candidate. That data showed a single shRNA can target two independent genes (MICA/MICB) to improve the phenotype of the CAR T cells.
shRNA stands for short hairpin RNA, part of the company’s proprietary non-gene edited technology platform.
In a January 10, 2022 outlook report, Petti said, “Our leading clinical CAR T assets, novel shRNA platform and foundational intellectual property within the allogeneic landscape has attracted widespread industry attention including most recently from Fortress Investment Group, which invested $32.5 million into the company. We believe our cutting-edge research in the allogeneic CAR T field supported by clinical data presented at multiple medical conferences over the past year and combined with these broader resources place us on an accelerated path towards developing the therapeutic benefit of our extensive set of technologies.”
That private placement was conducted on Dec. 8, 2021. Celyad issued 6.5 million ordinary shares at $5 USD per share. The goal was to use the funds to advance CYAD-101 and CYAD-211, as well as other CAR T products in the preclinical pipeline.
CAR T products have been very successful in hematological cancers, but getting them to work in solid tumors has been much more difficult.
In June 2021, Tmunity Therapeutics halted the development of its CAR T product after two patients in a solid tumor trial died from immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is a well-known severe side effect linked to CAR T therapies.
At the time, Oz Azam, co-founder of Tmunity, said, “What we are discovering is that the cytokine profiles we see in solid tumors are completely different from hematologic cancers. We observed ICANS. And we had two patient deaths as a result of that. We navigated the first event and obviously saw the second event, and as a result of that we have shut down version one of that program and pivoted quickly to our second generation.”
In hematological cancers, CAR T was linked to cytokines release syndrome, the so-called “cytokine storms.” ICANS is macrophage activation, but with potentially deadly ramifications.
It’s not yet known if the Celyad fatalities are related to the therapy or ICANS. The company indicated they are informing regulatory authorities, who may require further precautions.
