A2 Bio Advances Solid Tumour CAR T Programme With New Responses

A2 Biotherapeutics (A2 Bio) has reported updated safety and efficacy findings from its Phase 1/2 EVEREST-2 and DENALI-1 clinical studies evaluating investigational logic-gated chimeric antigen receptor (CAR) T-cell therapies in advanced solid tumours. The findings include a complete response (CR) in a patient with non-small cell lung cancer (NSCLC), ongoing beyond 12 months, in EVEREST-2. DENALI-1 reported its first CR in metastatic anal cancer and a partial response (PR) in refractory head and neck squamous cell carcinoma (HNSCC).

The data will be presented at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), scheduled for November 4–8, 2026, in Phoenix, Arizona. The EVEREST-2 abstract (#559) was selected as a Top 150 Abstract.

EVEREST-2 Reports Complete Response in NSCLC

EVEREST-2 (NCT06051695) is a first-in-human, open-label Phase 1/2 study evaluating two investigational autologous CAR T-cell therapies, A2B694 and A2B543. Both candidates use A2 Bio’s Tmod™ platform, which combines an activator receptor targeting mesothelin (MSLN) with a blocker receptor recognising HLA-A02. The design aims to target tumour cells that have lost HLA-A02 expression while protecting normal cells retaining the marker.

A2B543 additionally incorporates an NFAT-driven, membrane-tethered interleukin-12 (mem-IL-12) booster intended to enhance CAR T-cell potency and persistence while limiting systemic IL-12 exposure.

As of September 1, 2026, 16 patients had enrolled, including 13 receiving A2B694 and three receiving A2B543. The study included patients with colorectal, pancreatic, ovarian, gastroesophageal, mesothelioma and NSCLC.

Both therapies demonstrated manageable safety, with no dose-limiting toxicities (DLTs) or grade 4 treatment-related adverse events. In the A2B694 arm, one patient experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), while another experienced grade 1 ICANS and a third experienced grade 1 cytokine release syndrome (CRS). One grade 1 CRS event was reported with A2B543.

Among 13 efficacy-evaluable patients receiving A2B694, the best responses included one CR, eight cases of stable disease (SD) and four cases of progressive disease (PD). The CR occurred in a patient with NSCLC and was assessed at Day 90 according to RECIST 1.1, with confirmation by independent central review. The response remained ongoing beyond 12 months of follow-up.

Both efficacy-evaluable patients receiving A2B543, who had pancreatic cancer, achieved SD. The treatment was also associated with higher Tmod™ expansion than that observed in most A2B694-treated patients. Serum IL-12 levels remained below 5 pg/mL through Day 56 in both patients. The maximum tolerated dose has not yet been reached.

DENALI-1 Reports Responses in Anal and Head and Neck Cancers

DENALI-1 (NCT06682793) is a first-in-human, open-label Phase 1/2 study evaluating A2B395, an investigational allogeneic CAR T-cell therapy in adults with previously treated EGFR-positive advanced solid tumours.

A2B395 combines an EGFR-targeting activator with an HLA-A*02 blocker designed to mitigate graft-versus-host disease (GVHD) risk and reduce on-target, off-tumour toxicity. Unlike autologous CAR T-cell therapies, this approach does not require patient-specific leukapheresis.

As of August 21, 2026, 11 patients had received A2B395, including patients with anal, HNSCC, NSCLC, colorectal and breast cancers. No DLTs, GVHD or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) were reported. Two patients experienced CRS, including one grade 1 and one grade 2 event, both of which resolved.

Among nine efficacy-evaluable patients, the best responses included one CR, one PR, five cases of SD and two cases of PD, resulting in a disease control rate of 78%.

The CR occurred in a patient with unresectable anal cancer who had previously received five chemotherapy regimens and two courses of radiation therapy. Following treatment at dose level 3, the patient achieved a CR at Day 28, with resolution of all target and non-target lesions and no serious adverse events.

A heavily pretreated patient with refractory HNSCC achieved a PR at Day 180 following treatment at dose level 2. Disease control continued for six months, accompanied by resolution of tumour-related pain and improved quality of life, allowing the patient to return to work.

Tmod Platform Targets Tumour Selectivity in Solid Cancers

A2 Bio’s Tmod™ platform uses a dual-receptor logic-gate approach to distinguish tumour cells from normal tissues based on antigen expression and HLA status. In eligible patients, tumours lose HLA-A02 expression through loss of heterozygosity (LOH), allowing the activator to recognise tumour-associated antigens while the blocker protects normal cells retaining HLA-A02.

BASECAMP-1 (NCT04981119) is a master prescreening study that uses next-generation sequencing to identify patients with HLA LOH for potential enrolment in the therapeutic programmes.

EVEREST-2 evaluates autologous MSLN-targeted therapies, whereas DENALI-1 investigates an allogeneic EGFR-targeted approach. Both programmes seek to address challenges associated with CAR T-cell treatment of solid tumours, particularly tumour selectivity and treatment-related toxicity.

Early Clinical Findings Support Further Evaluation

The updated findings provide early evidence of antitumour activity across multiple advanced solid tumour types. Complete responses in NSCLC and metastatic anal cancer, together with a partial response in refractory HNSCC, highlight the potential of A2 Bio’s logic-gated CAR T-cell approach.

However, both programmes remain in early-phase development with small patient populations. Further enrolment and follow-up will be necessary to establish response durability, characterise safety and determine appropriate dosing before the therapeutic potential of these investigational therapies can be established.

References

A2 Biotherapeutics Presents Updated Safety and Efficacy Data from EVEREST-2 and DENALI-1 Clinical Studies during 2026 Annual Meeting of the Society for Immunotherapy of Cancer, A2 Bio, 03 November 2026

A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants with Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression (EVEREST-2), ClinicalTrials.gov ID NCT06051695

A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants with Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression (DENALI-1), ClinicalTrials.gov ID NCT06682793

Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing (BASECAMP-1), ClinicalTrials.gov ID NCT04981119