An Open-Label Phase 1a/1b Dose-Escalation and Expansion Study Investigating the Safety, Pharmacokinetics, Pharmacodynamics, and Activity of AB248 Alone or in Combination with Pembrolizumab in Adult Patients with Locally Advanced or Metastatic Solid Tumors

Overview

Etakafusp alfa, formerly known as AB248, is an investigational immunotherapy developed by Asher Biotherapeutics. It is designed to selectively activate CD8+ T cells, which are crucial for anti-tumor responses, while minimizing effects on regulatory T cells (Tregs) and natural killer (NK) cells to reduce potential toxicities. (asherbio.com)

Mechanism of Action

Etakafusp alfa is a fusion protein that targets the interleukin-2 (IL-2) pathway specifically in CD8+ T cells. By employing cis-targeting technology, it enhances the proliferation and activation of these cells, aiming to improve anti-tumor immunity without the adverse effects associated with non-selective IL-2 therapies. (asherbio.com)

Clinical Trials

Phase 1a/1b Trial

An open-label Phase 1a/1b clinical trial (NCT05653882) is currently underway to evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of etakafusp alfa, both as a monotherapy and in combination with pembrolizumab (KEYTRUDA®). This study includes patients with locally advanced or metastatic solid tumors, such as melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and squamous cell carcinoma of the head and neck (SCCHN). (asherbio.com)

Combination Studies

• NSCLC: In January 2025, Asher Bio announced a clinical supply agreement with AstraZeneca to evaluate etakafusp alfa in combination with rilvegostomig, a PD-1/TIGIT bispecific antibody, as a first-line treatment for advanced or metastatic NSCLC. (asherbio.com)

• Small Cell Lung Cancer (SCLC): A collaboration with Amgen was established to assess etakafusp alfa in combination with tarlatamab (IMDELLTRA®), a DLL3-targeting bispecific T-cell engager, in patients with extensive-stage SCLC. (asherbio.com)

Efficacy

Initial pharmacokinetic and pharmacodynamic data from the ongoing Phase 1a/1b trial have demonstrated proof of mechanism, showing selective activation of CD8+ T cells without substantial changes to Treg and NK cell numbers. Early evidence indicates anti-tumor activity, including confirmed objective responses. (asherbio.com)

Safety

Etakafusp alfa has exhibited a well-tolerated safety profile in early clinical evaluations. The selective activation of CD8+ T cells aims to reduce the off-target toxicities commonly associated with broader IL-2 therapies. (asherbio.com)

Further Reading

• Asher Bio Pipeline Overview
• ClinicalTrials.gov: NCT05653882

Last updated: Aug 2025

Inclusion Criteria:

* Age ≥18 years of age at the time consent is signed.

* Has adequate end organ function per laboratory testing.

* Pregnancy prevention requirements

* Has measurable disease per RECIST 1.1 as assessed by the local site Investigator/radiology.

* Has a performance status of 0 or 1 on Eastern Cooperative Oncology Group scale.

* Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts

Exclusion Criteria:

* Has a diagnosis of immunodeficiency.

* Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years.

* Has known active CNS metastases and/or carcinomatous meningitis.

* Has an active autoimmune disease that has required systemic treatment in the past 2 years.

* Has an active infection requiring systemic therapy.

* Inability to comply with study and follow-up procedures.

* Has had a severe hypersensitivity reaction (Grade ≥3) to treatment with pembrolizumab, another monoclonal antibody, or has history of any hypersensitivity to any components of the study treatments or any of their excipients.

* Has received prior systemic anticancer therapy including investigational agents within 4 weeks (or, if shorter, within 5 half-lives for kinase inhibitors) prior to first dose of study treatment.

* Has received prior radiotherapy within 2 weeks of start of study treatment or has had a history of radiation pneumonitis.

* Receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.

* Has received previous treatment with another agent targeting the IL-2, IL-7, or IL-15 receptors.

* Is expected to require any other form of antineoplastic therapy while on study