Achilles Therapeutics Makes Progress in Phase 1/2a Clinical Trials for Neoantigen Reactive T-Cell Therapy in NSCLC and Melanoma
The company noted that the first 3 patients with enhanced host conditioning have been dosed in the CHIRON and THETIS trials evaluating ATL001.
Achilles Therapeutics has dosed the first patients with enhanced host conditioning (EHC) in its phase 1/2 CHIRON study (NCT04032847) in non-small cell lung cancer (NSCLC) and its phase 1/2 THETIS study (NCT03997474) in melanoma, which are both evaluating ATL001, a clonal neoantigen reactive T-cell (cNeT) therapy, for the treatment of the aforementioned cancers, respectively.1
The company noted that the first 3 patients with EHC have been dosed in CHIRON and THETIS and that improved cNeT persistence and engraftment was observed in these patients. Achilles additionally stated that it has delivered 10 products containing more than 100 million cNeT and 5 products containing more than 1 billion cNeT. The company also pointed out that it anticipates announcing results from CHIRON and THETIS, including clinical activity and translational science findings with regard to potential EHC benefit, before the end of this year.
Alongside the update regarding these trials, Achilles also announced a new collaboration with Arcturus Therapeutics. The research collaboration will utilize Achille’s artificial intelligence-powered, tumor targeting technology and Arcturus’ self-amplifying mRNA platform in pursuit of evaluating the potential of second-generation mRNA cancer vaccines.
“During the second quarter we shared interim phase 1/2a data from our ongoing CHIRON and THETIS tumor infiltrating lymphocyte (TIL)-based cNeT clinical trials and established an important research collaboration with Arcturus Therapeutics to explore the use of clonal neoantigens in second-generation personalized mRNA cancer vaccines”, Iraj Ali, PhD, the chief executive officer of Achilles Therapeutics, said in a statement.1 “Our insights into the factors that drive durable engraftment and immune evasion led us to add an additional cohort in the CHIRON and THETIS trials to evaluate cNeT persistence and clinical activity in patients with EHC. These findings, along with the cancer vaccine research collaboration, continue to illustrate the potential value of our platform, including the unparalleled capability of PELEUS to select tumor targets with the highest potential for immune system recognition in a variety of modalities including TIL, neoantigen vaccines, antibody drug conjugates, and T-cell receptor T-cell therapies.”
Achilles Therapeutics previously presented early efficacy data from CHIRON and THETIS at the ESMO Immuno-Oncology Congress 2022, taking place December 7-9 in Geneva, Switzerland.2 In patients with NSCLC in CHIRON, investigators observed 1 partial response and 6 cases of stable disease for a 71% overall durable clinical benefit rate at 12 weeks. Half of patients with melanoma had stable disease.
“In addition to the durable clinical benefit, our translational science platform begins to deliver key mechanistic insights for our cNeT therapy that are not possible with a standard TIL product, including assessment of phenotypic markers as well as proliferative and cytolytic capacity of the tumor reactive cNeT component,” Sergio Quezada, PhD, chief scientific officer, Achilles, said in a statement at the time.2 “By virtue of knowing the cNeT targets and being able to characterize and track specific cNeT in the product and in the blood of patients, we can monitor cNeT dose, markers of function and exhaustion, engraftment, activation, and other features related to the patient, product, and performance in vivo.”
Achilles is not the only company currently evaluating a novel cell therapy product for the treatment of NSCLC. Notably, just earlier this month, Kiromic BioPharma announced that it had received fast track designation from the FDA for KB-GDT-01 (Deltacel), its investigational allogeneic gamma delta T-cell therapy being evaluated in the phase 1/2 Deltacel-01 clinical trial (NCT06069570) for the treatment of NSCLC.3
