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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Solid Tumor; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Biological: pembrolizumab; Biological: etakafusp alfa (AB248)

• Study Type: Interventional
• Enrollment (Estimated): 552
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Diego, California, United States, 92037
      • UCSD
    • San Francisco, California, United States, 94143
      • UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Health
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: etakafusp alfa (AB248) Monotherapy Dose-Escalation; etakafusp alfa (AB248) will be administered intravenously as a single agent	Biological: etakafusp alfa (AB248); Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug
Experimental: etakafusp alfa (AB248) + pembrolizumab Combination Dose-Escalation; etakafusp alfa (AB248) and pembrolizumab will be administered intravenously	Biological: pembrolizumab; Intravenous infusion of pembrolizumab; Other Names: KEYTRUDA®; Biological: etakafusp alfa (AB248); Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug
Experimental: etakafusp alfa (AB248) Monotherapy Indication Expansion; etakafusp alfa (AB248) will be administered intravenously as a single agent in disease specific cohorts	Biological: etakafusp alfa (AB248); Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug
Experimental: etakafusp alfa (AB248) + pembrolizumab Combination Indication Expansion; etakafusp alfa (AB248) and pembrolizumab will be administered intravenously in disease specific cohorts	Biological: pembrolizumab; Intravenous infusion of pembrolizumab; Other Names: KEYTRUDA®; Biological: etakafusp alfa (AB248); Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Serious Adverse Events (SAEs)	Based on toxicities observed	Signed consent up to 90 days after discontinuing study treatment
Frequency of Treatment Emergent Adverse Events (TEAEs)	Based on toxicities observed	Study Day 1 up to 90 days after discontinuing study treatment
Frequency of Adverse Events of Special Interest (AESIs)	Based on toxicities observed	Study Day 1 up to 90 days after discontinuing study treatment
Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death	Based on toxicities observed	Signed consent up to 90 days after discontinuing study treatment
Frequency of Dose-Limiting Toxicities (DLTs)	Based on toxicities observed	From Study Day 1 through up to Day 21, Day 28, or Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) according to RECIST version 1.1	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.	Study Day 1 up to approximately 24 months
Duration of Response (DOR) according to RECIST version 1.1	Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.	Study Day 1 up to approximately 24 months
Disease Control Rate (DCR) according to RECIST version 1.1	Defined as the percentage of patients who have achieved CR, PR, or stable disease.	Study Day 1 up to approximately 24 months
Progression-Free Survival (PFS) according to RECIST version 1.1	Defined as the time from first dose of AB248 to first documentation of radiographic disease progression or death, whichever occurs first	Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months
Overall Survival (OS) according to RECIST version 1.1	Defined as the time from first dose of AB248 to the date of death.	Study Day 1 up to time of death, assessed up to approximately 24 months
Maximum observed blood concentration (Cmax) of AB248	Defined as assessments for measuring maximum blood concentration of AB248	Study Day 1 up to approximately 24 months
AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248	Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC)	Study Day 1 up to approximately 24 months
Elimination half-life (t1/2) of AB248	Defined as the time required for half of the drug to be eliminated from the blood	Study Day 1 up to approximately 24 months
Quantification of peripheral blood CD8+ T cell pharmacodynamics	Defined as the volumetric enumeration of CD8+ T cells in whole blood as assessed by flow cytometry	Study Day 1 up to approximately 24 months
Changes in CD8+ T cell density in tumor tissues	Defined as changes in immune-staining for CD8+ T cells density in tumor tissue from patients providing paired biopsies.	Study Day 1 to approximately 1 month
Frequency of anti-drug antibodies (ADA)s to AB248	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.	Study Day 1 up to approximately 24 months

Collaborators and Investigators

• Sponsor: Asher Biotherapeutics, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Monitor, Asher Biotherapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: AB248-101; KEYNOTE-E29 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-E29 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No