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

Primary Purpose

Solid Tumor, Non Small Cell Lung Cancer, Melanoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AB248
Pembrolizumab
Sponsored by
Asher Biotherapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Investigational Site 002Recruiting
  • Investigational Site 009Recruiting
  • Invesigational Site 004Recruiting
  • Investigational Site 011Recruiting
  • Investigational Site 005Recruiting
  • Investigational Site 001Recruiting
  • Investigational site 012Recruiting
  • Investigational Site 008Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

AB248 Monotherapy Dose-Escalation

AB248 + Pembrolizumab Combination Dose-Escalation

AB248 Monotherapy Indication Expansion

AB248 + Pembrolizumab Combination Indication Expansion

Arm Description

AB248 will be administered intravenously as a single agent

AB248 and pembrolizumab will be administered intravenously

AB248 will be administered intravenously as a single agent in disease specific cohorts

AB248 and pembrolizumab will be administered intravenously in disease specific cohorts

Outcomes

Primary Outcome Measures

Frequency of Dose-Limiting Toxicities (DLTs)
Based on toxicities observed
Frequency of Serious Adverse Events (SAEs)
Based on toxicities observed
Frequency of Treatment Emergent Adverse Events (TEAEs)
Based on toxicities observed
Frequency of Adverse Events of Special Interest (AESIs)
Based on toxicities observed
Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death
Based on toxicities observed

Secondary Outcome Measures

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.
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.
Disease Control Rate (DCR) according to RECIST version 1.1
Defined as the percentage of patients who have achieved CR, PR, or stable disease.
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
Overall Survival (OS) according to RECIST version 1.1
Defined as the time from first dose of AB248 to the date of death.
Maximum observed blood concentration (Cmax) of AB248
Defined as assessments for measuring maximum blood concentration of AB248
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)
Elimination half-life (t1/2) of AB248
Defined as the time required for half of the drug to be eliminated from the blood
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
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.
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.

Full Information

First Posted
November 30, 2022
Last Updated
October 4, 2023
Sponsor
Asher Biotherapeutics, Inc.
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05653882
Brief Title
A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2023 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Asher Biotherapeutics, Inc.
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Non Small Cell Lung Cancer, Melanoma, Squamous Cell Carcinoma of Head and Neck, Renal Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
262 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AB248 Monotherapy Dose-Escalation
Arm Type
Experimental
Arm Description
AB248 will be administered intravenously as a single agent
Arm Title
AB248 + Pembrolizumab Combination Dose-Escalation
Arm Type
Experimental
Arm Description
AB248 and pembrolizumab will be administered intravenously
Arm Title
AB248 Monotherapy Indication Expansion
Arm Type
Experimental
Arm Description
AB248 will be administered intravenously as a single agent in disease specific cohorts
Arm Title
AB248 + Pembrolizumab Combination Indication Expansion
Arm Type
Experimental
Arm Description
AB248 and pembrolizumab will be administered intravenously in disease specific cohorts
Intervention Type
Biological
Intervention Name(s)
AB248
Intervention Description
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Intervention Description
Intravenous infusion of pembrolizumab
Primary Outcome Measure Information:
Title
Frequency of Dose-Limiting Toxicities (DLTs)
Description
Based on toxicities observed
Time Frame
From Study Day 1 through up to Day 21
Title
Frequency of Serious Adverse Events (SAEs)
Description
Based on toxicities observed
Time Frame
Signed consent up to 90 days after discontinuing study treatment
Title
Frequency of Treatment Emergent Adverse Events (TEAEs)
Description
Based on toxicities observed
Time Frame
Study Day 1 up to 90 days after discontinuing study treatment
Title
Frequency of Adverse Events of Special Interest (AESIs)
Description
Based on toxicities observed
Time Frame
Study Day 1 up to 90 days after discontinuing study treatment
Title
Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death
Description
Based on toxicities observed
Time Frame
Signed consent up to 90 days after discontinuing study treatment
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) according to RECIST version 1.1
Description
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.
Time Frame
Study Day 1 up to approximately 24 months
Title
Duration of Response (DOR) according to RECIST version 1.1
Description
Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.
Time Frame
Study Day 1 up to approximately 24 months
Title
Disease Control Rate (DCR) according to RECIST version 1.1
Description
Defined as the percentage of patients who have achieved CR, PR, or stable disease.
Time Frame
Study Day 1 up to approximately 24 months
Title
Progression-Free Survival (PFS) according to RECIST version 1.1
Description
Defined as the time from first dose of AB248 to first documentation of radiographic disease progression or death, whichever occurs first
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
Title
Overall Survival (OS) according to RECIST version 1.1
Description
Defined as the time from first dose of AB248 to the date of death.
Time Frame
Study Day 1 up to time of death, assessed up to approximately 24 months
Title
Maximum observed blood concentration (Cmax) of AB248
Description
Defined as assessments for measuring maximum blood concentration of AB248
Time Frame
Study Day 1 up to approximately 24 months
Title
AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248
Description
Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC)
Time Frame
Study Day 1 up to approximately 24 months
Title
Elimination half-life (t1/2) of AB248
Description
Defined as the time required for half of the drug to be eliminated from the blood
Time Frame
Study Day 1 up to approximately 24 months
Title
Quantification of peripheral blood CD8+ T cell pharmacodynamics
Description
Defined as the volumetric enumeration of CD8+ T cells in whole blood as assessed by flow cytometry
Time Frame
Study Day 1 up to approximately 24 months
Title
Changes in CD8+ T cell density in tumor tissues
Description
Defined as changes in immune-staining for CD8+ T cells density in tumor tissue from patients providing paired biopsies.
Time Frame
Study Day 1 to approximately 1 month
Title
Frequency of anti-drug antibodies (ADA)s to AB248
Description
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.
Time Frame
Study Day 1 up to approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations
Phone
650-628-8110
Email
clinops@asherbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Science & Operations
Organizational Affiliation
Asher Biotherapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site 002
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site 009
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Name
Invesigational Site 004
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site 011
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site 005
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site 001
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational site 012
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site 008
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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