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

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ClinicalTrials.gov Identifier: NCT05653882
Recruitment Status : Recruiting
First Posted : December 16, 2022
Last Update Posted : May 3, 2023
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Asher Biotherapeutics, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumor Non Small Cell Lung Cancer Melanoma Squamous Cell Carcinoma of Head and Neck Renal Cell Carcinoma Biological: AB248 Biological: Pembrolizumab Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 262 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 4, 2023
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : October 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AB248 Monotherapy Dose-Escalation
AB248 will be administered intravenously as a single agent
 Biological: AB248
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug
Experimental: AB248 + Pembrolizumab Combination Dose-Escalation
AB248 and pembrolizumab will be administered intravenously
 Biological: AB248
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug

Biological: Pembrolizumab
Intravenous infusion of pembrolizumab
Experimental: AB248 Monotherapy Indication Expansion
AB248 will be administered intravenously as a single agent in disease specific cohorts
 Biological: AB248
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug
Experimental: AB248 + Pembrolizumab Combination Indication Expansion
AB248 and pembrolizumab will be administered intravenously in disease specific cohorts
 Biological: AB248
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug

Biological: Pembrolizumab
Intravenous infusion of pembrolizumab


Outcome Measures
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Primary Outcome Measures :
  1. Frequency of Dose-Limiting Toxicities (DLTs) [ Time Frame: From Study Day 1 through up to Day 21 ]
    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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05653882


Contacts
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Contact: Clinical Operations 650-628-8110 clinops@asherbio.com

Locations
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United States, California
Investigational Site 002 Recruiting
Los Angeles, California, United States, 90095
United States, Indiana
Investigational Site 005 Recruiting
Lafayette, Indiana, United States, 47905
United States, Massachusetts
Investigational Site 001 Recruiting
Boston, Massachusetts, United States, 02215
United States, Tennessee
Investigational Site 008 Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Asher Biotherapeutics, Inc.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Clinical Science & Operations Asher Biotherapeutics, Inc.
More Information
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Responsible Party: Asher Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05653882    
Other Study ID Numbers: AB248-101
KEYNOTE-E29 ( Other Identifier: Merck Sharp & Dohme, LLC )
First Posted: December 16, 2022    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
 Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Head and Neck Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action