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Active, Not Recruiting

NCT Number: NCT05653882

A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors

This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of AB248 as monotherapy OR in combination with pembrolizumab in adult participants with locally advanced or metastatic solid tumors. The study will consist of a dose escalation and a dose expansion stage.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

etakafusp alfa (AB248)

Biological

Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug

Pembrolizumab

Biological

Intravenous infusion of pembrolizumab

Other names: KEYTRUDA®

Primary outcomes

  1. Frequency of Dose-Limiting Toxicities (DLTs)

    Time frame: From Study Day 1 through up to Day 21, Day 28, or Day 42

    Based on toxicities observed

  2. Frequency of Serious Adverse Events (SAEs)

    Time frame: Signed consent up to 90 days after discontinuing study treatment

    Based on toxicities observed

  3. Frequency of Treatment Emergent Adverse Events (TEAEs)

    Time frame: Study Day 1 up to 90 days after discontinuing study treatment

    Based on toxicities observed

  4. Frequency of Adverse Events of Special Interest (AESIs)

    Time frame: Study Day 1 up to 90 days after discontinuing study treatment

    Based on toxicities observed

  5. Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death

    Time frame: Signed consent up to 90 days after discontinuing study treatment

    Based on toxicities observed

Secondary outcomes

  1. Objective Response Rate (ORR) according to RECIST version 1.1

    Time frame: Study Day 1 up to approximately 24 months

    Defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR); a confirmed response is a response that persists on repeat-imaging ≥4 weeks after initial documentation of response.

  2. Duration of Response (DOR) according to RECIST version 1.1

    Time frame: Study Day 1 up to approximately 24 months

    Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.

  3. Disease Control Rate (DCR) according to RECIST version 1.1

    Time frame: Study Day 1 up to approximately 24 months

    Defined as the percentage of patients who have achieved CR, PR, or stable disease.

  4. Progression-Free Survival (PFS) according to RECIST version 1.1

    Time frame: Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months

    Defined as the time from first dose of AB248 to first documentation of radiographic disease progression or death, whichever occurs first

  5. Overall Survival (OS) according to RECIST version 1.1

    Time frame: Study Day 1 up to time of death, assessed up to approximately 24 months

    Defined as the time from first dose of AB248 to the date of death.

  6. Maximum observed blood concentration (Cmax) of AB248

    Time frame: Study Day 1 up to approximately 24 months

    Defined as assessments for measuring maximum blood concentration of AB248

  7. AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248

    Time frame: Study Day 1 up to approximately 24 months

    Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC)

  8. Elimination half-life (t1/2) of AB248

    Time frame: Study Day 1 up to approximately 24 months

    Defined as the time required for half of the drug to be eliminated from the blood

  9. Quantification of peripheral blood CD8+ T cell pharmacodynamics

    Time frame: Study Day 1 up to approximately 24 months

    Defined as the volumetric enumeration of CD8+ T cells in whole blood as assessed by flow cytometry

  10. Changes in CD8+ T cell density in tumor tissues

    Time frame: Study Day 1 to approximately 1 month

    Defined as changes in immune-staining for CD8+ T cells density in tumor tissue from patients providing paired biopsies.

  11. Frequency of anti-drug antibodies (ADA)s to AB248

    Time frame: Study Day 1 up to approximately 24 months

    Defined as the frequency of ADA formation for immunogenicity assessments evaluated during study treatment up until 30 days after the final dose of study treatment.

Sponsors and collaborators

Lead sponsor

Asher Biotherapeutics, Inc.

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Dec 16, 2022
Registry last updated
Sep 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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