A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors
- 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.
- Short title
- 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
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Active, not recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2027-05-01
- First posted
- 2022-12-16
- Registry last updated
- 2025-09-10
- Primary completion date
- 2026-08-01
- Start date
- 2023-01-04
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Asher Biotherapeutics, Inc.
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05653882
- ClinicalTrials.gov ID
- NCT05653882
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Frequency of Dose-Limiting Toxicities (DLTs)
Timeframe: From Study Day 1 through up to Day 21, Day 28, or Day 42
Based on toxicities observed
Frequency of Serious Adverse Events (SAEs)
Timeframe: Signed consent up to 90 days after discontinuing study treatment
Based on toxicities observed
Frequency of Treatment Emergent Adverse Events (TEAEs)
Timeframe: Study Day 1 up to 90 days after discontinuing study treatment
Based on toxicities observed
Frequency of Adverse Events of Special Interest (AESIs)
Timeframe: 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
Timeframe: Signed consent up to 90 days after discontinuing study treatment
Based on toxicities observed
Objective Response Rate (ORR) according to RECIST version 1.1
Timeframe: 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.
Duration of Response (DOR) according to RECIST version 1.1
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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.
Maximum observed blood concentration (Cmax) of AB248
Timeframe: 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
Timeframe: 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
Timeframe: Study Day 1 up to approximately 24 months
Defined as the time required for half of the drug to be eliminated from the blood
Quantification of peripheral blood CD8+ T cell pharmacodynamics
Timeframe: 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
Changes in CD8+ T cell density in tumor tissues
Timeframe: 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
Timeframe: 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.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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
- 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
- City of HopeDuarte, United States
- UCLALos Angeles, United States
- UCSDSan Diego, United States
- UCSFSan Francisco, United States
- YaleNew Haven, United States
- University of MiamiMiami, United States
- Ocala Oncology CenterOcala, United States
- University of Chicago Medical CenterChicago, United States
- Massachusetts General HospitalBoston, United States
- Dana Farber Cancer InstituteBoston, United States
- Karmanos Cancer InstituteDetroit, United States
- Washington UniversitySt Louis, United States
- RutgersNew Brunswick, United States
- NYUNew York, United States
- Memorial Sloan Kettering Cancer CenterNew York, United States
- UNC Lineberger Comprehensive Cancer CenterChapel Hill, United States
- Providence Cancer Institute Franz ClinicPortland, United States
- Sarah Cannon Research InstituteNashville, United States
- Intermountain HealthMurray, United States
- Virginia CommonwealthRichmond, United States
Other registry identifiers
- KEYNOTE-E29