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

Phase 1Active Not RecruitingNCT05653882

Asher Biotherapeutics, Inc.552 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

552

Conditions

Solid Tumor Non Small Cell Lung Cancer Melanoma Squamous Cell Carcinoma of Head and Neck Renal Cell Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

City of Hope

Duarte, California, United States

UCLA

Los Angeles, California, United States

UCSD

San Diego, California, United States

UCSF

San Francisco, California, United States

Yale

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

Ocala Oncology Center

Ocala, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

...and 10 more locations

Outcomes

Primary Outcomes

Frequency of Dose-Limiting Toxicities (DLTs)

Based on toxicities observed

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

Frequency of Serious Adverse Events (SAEs)

Based on toxicities observed

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

Frequency of Treatment Emergent Adverse Events (TEAEs)

Based on toxicities observed

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

Frequency of Adverse Events of Special Interest (AESIs)

Based on toxicities observed

Time frame: 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

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

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

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

Overall Survival (OS) according to RECIST version 1.1

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

Maximum observed blood concentration (Cmax) of AB248

Defined as assessments for measuring maximum blood concentration of AB248

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: Study Day 1 up to approximately 24 months

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

Overview

Conditions

Interventions

Eligibility

Locations (20)

Outcomes

Primary Outcomes

Secondary Outcomes