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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: AB248
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AB248 Monotherapy Dose-Escalation<br>AB248 will be administered intravenously as a single agent | Biological: AB248<br>* Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug<br>|
| Experimental: AB248 + Pembrolizumab Combination Dose-Escalation<br>AB248 and pembrolizumab will be administered intravenously | Biological: AB248<br>* Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug<br>Biological: Pembrolizumab<br>* Intravenous infusion of pembrolizumab<br>|
| Experimental: AB248 Monotherapy Indication Expansion<br>AB248 will be administered intravenously as a single agent in disease specific cohorts | Biological: AB248<br>* Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug<br>|
| Experimental: AB248 + Pembrolizumab Combination Indication Expansion<br>AB248 and pembrolizumab will be administered intravenously in disease specific cohorts | Biological: AB248<br>* Intravenous infusion of AB248: CD8+ T cell selective interleukin-2 investigational drug<br>Biological: Pembrolizumab<br>* Intravenous infusion of pembrolizumab<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |