This is a Study to Evaluate the Safety and Tolerability of ABL503, and to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ABL503 in Subjects With Any Progressive Locally Advanced or Metastatic Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1 Dose Escalation and Expansion Study of ABL503, a Bispecific Antibody of 4-1BB and PD-L1, as a Single Agent in Subjects With Any Progressive Locally Advanced (Unresectable) or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04762641
• Other study ID #: ABL503-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: April 1, 2021
• Est. completion date: June 15, 2025

Study information

• Verified date: August 2023
• Source: ABL Bio, Inc.
• Contact: Juyeun Jeon
• Phone: +82-31-8014-7039
• Email: juyeun.jeon[@]ablbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a first-in-human Phase 1, single-arm, open-label, multicenter, multiple-dose, dose-escalation and dose-expansion study of ABL503 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, preliminary antitumor activity, and the PD effect of ABL503 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors who are relapsed or refractory following the last line of treatment and have no available standard of care option. This study includes 3 parts: a dose-escalation part, a dose-expansion part and tumor-expansion part

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and/or cytologically confirmed diagnosis of any progressive locally advanced (unresectable) or metastatic solid tumors that have relapsed or are refractory following the last line of treatment, for which prior standard therapy has been ineffective, standard therapy does not exist, or is not considered appropriate.
• With AE(s) excluding alopecia or Grade 2 toxicities that are deemed stable or irreversible (eg, peripheral neuropathy) from prior therapy that have improved to Grade 1 or the baseline grade more than 14 days prior to the first administration of the study drug
• Adequate hematologic, hepatic, and renal functions confirmed based on the screening laboratory tests and reconfirmed with additional safety laboratory tests performed within 72 hours prior to the first administration of ABL503

Exclusion Criteria:

• Prior anticancer monoclonal antibody treatment or investigational therapy within 28 days prior to the first administration of study drug or has not recovered (ie, = Grade 1 or at baseline grade) from AEs due to previously administered agent more than 14 days prior to ABL503 administration
• Prior chemotherapy or radiation therapy within 2 weeks or targeted small molecule therapy within 5 half-lives prior to the first administration of study drug or has not recovered (ie, = Grade 1 or at baseline grade) from AEs due to previously administered agent more than 14 days prior to ABL503 administration
• Requiring or received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration.
• Risk factors for bowel obstruction or bowel perforation (including but not limited to a history of acute diverticulitis, intra-abdominal abscess, and abdominal carcinomatosis.
• Discontinued from prior immunomodulatory therapy due to any intolerable immune-related adverse events (IrAEs) requiring systemic steroid treatment
• History of drug-induced pneumonitis (interstitial lung disease) or currently has pneumonitis
• Received prior treatment with an anti-4-1BB antibody

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• ABL503
ABL503 will be administered intravenously (IV) on Day 1 and Day 15 of every 28-day cycle in the dose-escalation part. The dosing interval to be used in the dose-expansion part will be re-evaluated based on the emerging safety and PK data from the dose-escalation part of the study.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	City of Hope	Duarte	California
United States	USC	Los Angeles	California
United States	NEXT Oncology	San Antonio	Texas
United States	UCLA	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
ABL Bio, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects with Dose-Limiting Toxicities (DLT)	Number of subjects with Dose-Limiting Toxicity (DLT)	From Day 1 until disease progression or Day 28, whichever came first
Primary	Number of subjects with AE, IrAEs, IRRs, SAEs and abnormalities in Lab	Number of subjects with Adverse Event, Immune-related Adverse Event, Infusion-related Reactions (IRRs), serious AEs, and abnormalities in lab parameters	From Day 1 until confirmed CR, disease progression, initiation of a new anticancer therapy, unacceptable AEs, or subject's consent withdrawal, or investigator's decision to discontinue treatment, which came first, assessed up to approx. 12 months
Secondary	Objective Response Rate (ORR)	Proportion of subject with best overall response of complete response (CR) or partial response (PR) per RECIST v1.1	From Day 1 until confirmed CR, disease progression, initiation of a new anticancer therapy, unacceptable AEs, or subject's consent withdrawal, or investigator's decision to discontinue treatment, which came first, assessed up to approx. 12 months
Secondary	Pharmacokinetic (PK) of ABL503	Serum concentrations of ABL503 will be collected and analyzed to evaluate the PK of ABL503	From Day 1 until confirmed CR, disease progression, initiation of a new anticancer therapy, unacceptable AEs, or subject's consent withdrawal, or investigator's decision to discontinue treatment, which came first, assessed up to approx. 12 months
Secondary	Immunogenicity of ABL503	Incidence of anti-ABL503 antibody will be analyzed to evaluate the Immunogenicity of ABL503	From Day 1 until confirmed CR, disease progression, initiation of a new anticancer therapy, unacceptable AEs, or subject's consent withdrawal, or investigator's decision to discontinue treatment, which came first, assessed up to approx. 12 months