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

• ClinicalTrials.gov Identifier: NCT05653882
• Recruitment Status: Recruiting
• First Posted: December 16, 2022
• Last Update Posted: May 13, 2024
• Sponsor: Asher Biotherapeutics, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Asher Biotherapeutics, Inc.

Tracking Information

• First Submitted Date: November 30, 2022
• First Posted Date: December 16, 2022
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: January 4, 2023
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 8, 2022)

• Objective Response Rate (ORR) according to RECIST version 1.1 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
  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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: AB248 Monotherapy Dose-Escalation
  AB248 will be administered intravenously as a single agent
  Intervention: Biological: AB248
• Experimental: AB248 + pembrolizumab Combination Dose-Escalation
  AB248 and pembrolizumab will be administered intravenously
  Interventions:

  • Biological: AB248
  • Biological: pembrolizumab
• Experimental: AB248 Monotherapy Indication Expansion
  AB248 will be administered intravenously as a single agent in disease specific cohorts
  Intervention: Biological: AB248
• Experimental: AB248 + pembrolizumab Combination Indication Expansion
  AB248 and pembrolizumab will be administered intravenously in disease specific cohorts
  Interventions:

  • Biological: AB248
  • Biological: pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 9, 2024): 462
• Original Estimated Enrollment (submitted: December 8, 2022): 262
• Estimated Study Completion Date: May 2027
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Operations; 650-410-7588; clinops@asherbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05653882
• Other Study ID Numbers: AB248-101; KEYNOTE-E29 ( Other Identifier: Merck Sharp & Dohme, LLC ); MK-3475-E29 ( Other Identifier: Merck Sharp & Dohme, LLC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Asher Biotherapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Asher Biotherapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor; Asher Biotherapeutics, Inc.

• PRS Account: Asher Biotherapeutics, Inc.
• Verification Date: May 2024