Dosing begins with a trial of a new immunotherapy for the treatment of advanced solid tumors

A phase 1a/1b, first-in-human study of a new immunotherapy agent, AB248, has given the agent to the first patient with a locally advanced or metastatic solid tumor.

The first patient received a dose of a new therapy, AB248, as part of AB248-011 (NCT05653882) a phase 1a/1b study of immunotherapy in combination with pembrolizumab (Keytruda) for adult patients with locally advanced or metastatic solid tumors.1

The study consists of a dose-escalation phase and a dose-expansion phase to evaluate AB248 in combination with pembrolizumab for the treatment of patients from different treatment areas, including melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and squamous cell carcinoma of the head and neck (SCCHN ). Intravenous (IV) infusion of AB248 and IV pembrolizumab will be given to patients with NSCLC and SCCHN and will be titrated based on patient response to therapy.

“We are pleased to begin clinical evaluation of AB248, our most advanced product candidate,” said Dr. Craig Gibbs, chief executive officer of Asher Bio, in a press release announcing the initiation of the dose escalation and expansion portion of the trial. “This is a significant milestone for Asher Bio and our efforts to deliver a new class of therapies that address the limitations of existing immune-based drugs by specifically targeting and activating only the desired type of immune cells, thereby avoiding the pleiotropic effects that can diminish effectiveness and cause toxicity.”

The primary outcome of the study is to measure the incidence of dose-limiting toxicities (DLTs), serious adverse events (AEs), treatment-emergent adverse events, adverse events of special interest, and adverse events leading to discontinuation, treatment discontinuation, and death.

Secondary outcomes that researchers look at include measures of effectiveness, such as objective response rate and duration of response to treatment according to RECIST version 1.1. The researchers are also looking for results specific to the use of AB248. These include the maximum observed blood concentration, the area under the plasma concentration versus time curve, and the elimination half-life of AB248.

AB248 is a CD8-targeted interleukin-2 immunotherapy. It is designed to selectively and potently activate CD8+ T-cells while avoiding natural killer cells that act as a pharmacological drain and contribute to immunosuppressive toxicity. Preclinical studies have shown that AB248 has an approximately 1000-fold advantage for activating CD8+ T cells over natural killer cells and regulatory T cells.

Preclinical data presented at the 37th annual meeting of the Society for Immunotherapy of Cancer (SITC) showed that a murine surrogate for AB248, muAB248, had potent antitumor activity without weight loss and signs of tolerability.2 In a subset of murine tumor infiltrates, treatment with muAB248 showed expansion of several CD8+ T cell subsets, with similar results in cynomolgus monkeys.

In the human dose escalation trial, eligible patients include those previously treated with PD-1 therapy who now have advanced or metastatic disease. Patients must be 18 years of age or older and have adequate organ function and measurable disease according to RECIST 1.1. Moreover, they must have an ECOG performance status of 0 or 1, but will be excluded from the trial if they have a diagnosis of immunodeficiency.

The trial will follow a Bayesian optimal interval trial design and will enroll eligible patients at several dose levels and frequencies of AB248 monotherapy and in combination with pembrolizumab. Once the recommended dose is determined, the study will be expanded to indication-specific cohorts to evaluate AB248 as monotherapy and in combination with pembrolizumab.

“I am excited to begin administering AB248 to patients as part of this clinical trial,” said Elizabeth Buchbinder, MD, Dana-Farber Cancer Center, and an investigator in the phase 1a/1b clinical trial, in a press release. “Although there have been significant advances in the treatment of patients with locally advanced and metastatic solid tumors, many patients are still underserved by current options, particularly after immune checkpoint inhibitor therapy has failed. I am encouraged by the preclinical data supporting the differentiated profile of AB248 and look forward to working with Asher Bio and fellow clinical investigators to evaluate AB248 in this phase 1a/1b clinical trial.”


1. Asher Bio Announces Dosing of First Patient in Phase 1a/1b Clinical Trial of AB248, a cis-Targeted IL-2 Immunotherapy Candidate, for Treatment of Locally Advanced or Metastatic Solid Tumors. News. Asher Bio. January 17, 2023. Accessed January 18, 2023.

2. Asher Bio presents new preclinical data at SITC 2022 that further support the progress of AB248 and AB821 as highly differentiated cis-targeted cancer immunotherapies. News. Asher Bio. November 10, 2022. Accessed January 18, 2023.

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