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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05653882
• Other study ID #: AB248-101
• Secondary ID: KEYNOTE-E29MK-34
• Status: Recruiting
• Phase: Phase 1
• Start date: January 4, 2023
• Est. completion date: May 2027

Study information

• Verified date: May 2024
• Source: Asher Biotherapeutics, Inc.
• Contact: Clinical Operations
• Phone: 650-410-7588
• Email: clinops[@]asherbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 462
• Est. completion date: May 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• AB248
Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug
• pembrolizumab
Intravenous infusion of pembrolizumab

Locations

Country	Name	City	State
United States	Investigational Site 001	Boston	Massachusetts
United States	Investigational Site 014	Detroit	Michigan
United States	Investigational Site 005	Lafayette	Indiana
United States	Investigational Site 002	Los Angeles	California
United States	Investigational Site 011	Miami	Florida
United States	Investigational Site 008	Nashville	Tennessee
United States	Invesigational Site 004	New Haven	Connecticut
United States	Investigational Site 010	Ocala	Florida
United States	Investigational Site 012	Saint Louis	Missouri
United States	Investigational Site 009	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Asher Biotherapeutics, Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Dose-Limiting Toxicities (DLTs)	Based on toxicities observed	From Study Day 1 through up to Day 21
Primary	Frequency of Serious Adverse Events (SAEs)	Based on toxicities observed	Signed consent up to 90 days after discontinuing study treatment
Primary	Frequency of Treatment Emergent Adverse Events (TEAEs)	Based on toxicities observed	Study Day 1 up to 90 days after discontinuing study treatment
Primary	Frequency of Adverse Events of Special Interest (AESIs)	Based on toxicities observed	Study Day 1 up to 90 days after discontinuing study treatment
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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