Investigational Drug
AB248
TrialFetch AI Analysis
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Overview
AB248, now called etakafusp alfa, is an investigational CD8-targeted interleukin-2 (IL-2) fusion protein being developed for advanced solid tumors. It is under evaluation alone and with pembrolizumab in the ongoing Phase 1a/1b trial NCT05653882. Preliminary human results were reported at the 2026 ASCO Annual Meeting; no randomized efficacy results are available. (ascopubs.org)
Mechanism of action
AB248 combines an attenuated IL-2 mutein with an antibody targeting CD8β, concentrating IL-2 receptor signaling on CD8-positive T cells while limiting stimulation of regulatory T cells and natural killer cells. Preclinical studies found more than 500-fold greater potency for CD8-positive T cells than for other tested immune-cell populations. The molecule induced selective CD8 T-cell expansion and required additional T-cell-receptor signaling for full effector cytokine release. (aacrjournals.org)
Efficacy
As of December 1, 2025, 61 patients had received AB248 monotherapy and 68 had received AB248 plus pembrolizumab. Among heavily pretreated, response-evaluable melanoma patients:
- Cutaneous melanoma, higher-dose monotherapy: 2 confirmed partial responses among 11 patients (18%).
- Cutaneous melanoma, combination therapy: 2 confirmed partial responses among 16 patients (12%).
- Mucosal melanoma, combination therapy: 3 confirmed partial responses among 11 patients (27%).
- One additional patient with mucosal melanoma had stable disease lasting more than 15 months on monotherapy.
Most evaluable patients had previously received combination immunotherapy, making these preliminary signals notable but difficult to interpret without larger or controlled cohorts. Peripheral CD8-positive T cells expanded more than 20-fold at higher monotherapy doses and more than 11-fold at evaluated combination doses. (ascopubs.org)
Safety
The most common treatment-emergent adverse events across treatment groups were fatigue (50%), rash (49%), nausea (43%), chills (33%), fever (32%), vomiting (32%), and diarrhea (30%); more than 95% of these events were grade 1–2. Maximum tolerated doses were 0.5 mg/kg every two weeks for monotherapy and 0.15 mg/kg every three weeks with pembrolizumab. A maximum tolerated dose was not reached with step-up combination dosing. These findings remain preliminary, and detailed rates of serious or grade 3–4 toxicities were not provided in the published abstract. (ascopubs.org)
Further reading
- 2026 ASCO clinical-trial abstract
- Peer-reviewed preclinical characterization of AB248
- Study in human cancer tissue
- NCT05653882 trial record
Last updated: Sep 2026
Active trials using AB248
Found 2 active trials using this drug:
TrialFetch AI summary: Adults with extensive-stage small cell lung cancer that has progressed or recurred after at least one prior therapy receive tarlatamab plus intravenous AB248. Tarlatamab is a DLL3-targeted bispecific T-cell engager; AB248 is an investigational CD8β-targeted IL-2 fusion protein designed to preferentially stimulate CD8-positive T cells.
ClinicalTrials.gov ID: NCT07037758
TrialFetch AI summary: For adults with previously untreated stage IV squamous or nonsquamous NSCLC, PD-L1 TPS ≥1%, and no actionable alteration with approved first-line targeted therapy, this study evaluates rilvegostomig, an investigational PD-1/TIGIT bispecific antibody, combined with either AB248, a CD8-targeted IL-2 fusion protein, or platinum-based chemotherapy. Chemotherapy combinations include ramucirumab (anti-VEGFR2) in the squamous expansion cohort and are tested with or without it in nonsquamous disease.
ClinicalTrials.gov ID: NCT06996782
