Clinical trial NCT05653882: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Non Small Cell Lung Cancer
Melanoma
Squamous Cell Carcinoma of Head and Neck
Renal Cell Carcinoma
Lead sponsor: Asher Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-12-16
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
measure: Frequency of Dose-Limiting Toxicities (DLTs)
timeFrame: From Study Day 1 through up to Day 21, Day 28, or Day 42
measure: Frequency of Serious Adverse Events (SAEs)
timeFrame: Signed consent up to 90 days after discontinuing study treatment
measure: Frequency of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Study Day 1 up to 90 days after discontinuing study treatment
measure: Frequency of Adverse Events of Special Interest (AESIs)
timeFrame: Study Day 1 up to 90 days after discontinuing study treatment
measure: Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death
timeFrame: Signed consent up to 90 days after discontinuing study treatment
Secondary outcomes:
measure: Objective Response Rate (ORR) according to RECIST version 1.1
timeFrame: Study Day 1 up to approximately 24 months
measure: Duration of Response (DOR) according to RECIST version 1.1
timeFrame: Study Day 1 up to approximately 24 months
measure: Disease Control Rate (DCR) according to RECIST version 1.1
timeFrame: Study Day 1 up to approximately 24 months
measure: Progression-Free Survival (PFS) according to RECIST version 1.1
timeFrame: Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months
measure: Overall Survival (OS) according to RECIST version 1.1
timeFrame: Study Day 1 up to time of death, assessed up to approximately 24 months
measure: Maximum observed blood concentration (Cmax) of AB248
timeFrame: Study Day 1 up to approximately 24 months
measure: AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248
timeFrame: Study Day 1 up to approximately 24 months
measure: Elimination half-life (t1/2) of AB248
timeFrame: Study Day 1 up to approximately 24 months
measure: Quantification of peripheral blood CD8+ T cell pharmacodynamics
timeFrame: Study Day 1 up to approximately 24 months
measure: Changes in CD8+ T cell density in tumor tissues
timeFrame: Study Day 1 to approximately 1 month
measure: Frequency of anti-drug antibodies (ADA)s to AB248
timeFrame: Study Day 1 up to approximately 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Diego
country: United States
facility: UCSD
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers
state: New Jersey
city: New York
country: United States
facility: NYU
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Murray
country: United States
facility: Intermountain Health
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth
state: Virginia
Study officials:
affiliation: Asher Biotherapeutics, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: