Melanoma, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Solid Tumor, Squamous Cell Carcinoma of Head and Neck
Conditions
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.
Interventions
BIOLOGICALetakafusp alfa (AB248)
Intravenous infusion of etakafusp alfa (AB248): CD8+ T cell selective interleukin-2 investigational drug
BIOLOGICALpembrolizumab
Intravenous infusion of pembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Asher Biotherapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Dose-Limiting Toxicities (DLTs) | From Study Day 1 through up to Day 21, Day 28, or Day 42 | Based on toxicities observed |
| Frequency of Serious Adverse Events (SAEs) | Signed consent up to 90 days after discontinuing study treatment | Based on toxicities observed |
| Frequency of Treatment Emergent Adverse Events (TEAEs) | Study Day 1 up to 90 days after discontinuing study treatment | Based on toxicities observed |
| Frequency of Adverse Events of Special Interest (AESIs) | Study Day 1 up to 90 days after discontinuing study treatment | Based on toxicities observed |
| Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death | Signed consent up to 90 days after discontinuing study treatment | Based on toxicities observed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed blood concentration (Cmax) of AB248 | Study Day 1 up to approximately 24 months | Defined as assessments for measuring maximum blood concentration of AB248 |
| AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248 | Study Day 1 up to approximately 24 months | Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC) |
| Elimination half-life (t1/2) of AB248 | Study Day 1 up to approximately 24 months | Defined as the time required for half of the drug to be eliminated from the blood |
| Objective Response Rate (ORR) according to RECIST version 1.1 | Study Day 1 up to approximately 24 months | 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. |
| Changes in CD8+ T cell density in tumor tissues | Study Day 1 to approximately 1 month | 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 | Study Day 1 up to approximately 24 months | 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. |
| Quantification of peripheral blood CD8+ T cell pharmacodynamics | Study Day 1 up to approximately 24 months | Defined as the volumetric enumeration of CD8+ T cells in whole blood as assessed by flow cytometry |
| Duration of Response (DOR) according to RECIST version 1.1 | Study Day 1 up to approximately 24 months | 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 | Study Day 1 up to approximately 24 months | Defined as the percentage of patients who have achieved CR, PR, or stable disease. |
| Progression-Free Survival (PFS) according to RECIST version 1.1 | Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months | 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 | Study Day 1 up to time of death, assessed up to approximately 24 months | Defined as the time from first dose of AB248 to the date of death. |
Countries
United States
Outcome results
None listed