Further details on the KEYNOTE-B79 trial were presented at the 2022 ASCO GI Symposium.
The first patient has been dosed in the phase 1b KEYNOTE-B79 trial (NCT04991948) of the chimeric antigen receptor (CAR) T-cell therapy CYAD-101 (Celyad Oncology) in combination with pembrolizumab for refractory metastatic colorectal cancer (mCRC).1
Further details on the trial were presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers (GI) Symposium, January 20-22, 2022, by Richard D. Kim, MD, service chief, Medical Gastrointestinal Oncology and senior member, Gastrointestinal Oncology Department, Moffitt Cancer Center, and professor, oncology, University of South Florida College of Medicine.2
“[Evidence implied] that CYAD-101 may also be modulating the immune suppressive environment in patients mirroring what was demonstrated in pre-clinical models. We considered that a sequential therapy with the anti-PD1 monoclonal antibody pembrolizumab to further release the anti-tumor potential of this expanded T-cell population may drive deeper, more durable and new clinical responses beyond that currently demonstrated with the CAR T-cells alone,” Kim and colleagues wrote.2
KEYNOTE-B79 is evaluating the safety and efficacy of 3, bi-weekly, 1x109-cell infusions of CYAD-101 after FOLFOX preconditioning across 5 sites in the US and Europe.Participants will start 200 mg pembrolizumab treatment 3 weeks after last infusion, which will continue every 3 weeks for up to 2 years. The trial is enrolling participants with microsatellite stable/mismatch-repair proficient, relapsed/refractory mCRC after at least 1 metastatic line of therapy that included FOLFOX chemotherapy.
The trial’s primary endpoints are evaluating safety and efficacy via the occurrence of dose-limiting toxicities (DLTs) and objective response rate (ORR). ORR will be evaluated 6 weeks after first pembrolizumab treatment.Preliminary data from the trial are expected in the second half of 2022.3
Celyad Oncology is developing additional CAR T-cell therapies, including CYAD-211, an allogeneic shRNA-based anti-BCMA therapy for relapsed/refractory multiple myeloma, and CYAD-02, a next-generation, autologous NKG2D receptor therapy for acute myeloid leukemia and myelodysplastic syndrome.
Filippo Petti, chief executive officer, Celyad Oncology, commented on the company’s trials in a statement, saying, “The validation of our proprietary shRNA platform this past year represented an incredible achievement for the Company as we continued to strategically transform the organization to a fully allogeneic CAR T platform Company. The power and versatility of our shRNA platform, including the ability to multiplex and modulate the levels of gene expression, continues to support its strength, value, and potential differentiation within the allogenic cell therapy landscape. We believe our non-gene edited technologies are well-positioned to drive a major impact on the CAR T industry as the approach that does not have the risks associated with gene-editing technologies, including the potential for translocation adverse events.”3
CYAD-211 is being evaluated in the phase 1/2 IMMUNICY-1 trial (NCT04613557), which has so far demonstrated clinical activity with an acceptable safety profile. The phase 2 portion of the study will evaluate lymphodepleting regimens with the cell therapy. Additional data is expected mid-2022. CYAD-02 is being evaluated in the phase 1 CYCLE-1 trial (NCT04167696) which has demonstrated that a single shRNA can target both MICA and MICB, enhancing the cell therapy phenotype.
“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. This is an exciting time at Celyad Oncology and we look forward to building upon our recent accomplishments throughout 2022 and beyond,” Petti added to the statement.3