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

• ClinicalTrials.gov Identifier: NCT04762641
• Recruitment Status: Recruiting
• First Posted: February 21, 2021
• Last Update Posted: August 25, 2023
• Sponsor: ABL Bio, Inc.
• Information provided by (Responsible Party): ABL Bio, Inc.

Tracking Information

• First Submitted Date: January 28, 2021
• First Posted Date: February 21, 2021
• Last Update Posted Date: August 25, 2023
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: June 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2021)

• Number of Subjects with Dose-Limiting Toxicities (DLT) [ Time Frame: From Day 1 until disease progression or Day 28, whichever came first ]
  Number of subjects with Dose-Limiting Toxicity (DLT)
• Number of subjects with AE, IrAEs, IRRs, SAEs and abnormalities in Lab [ Time Frame: 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 ]
  Number of subjects with Adverse Event, Immune-related Adverse Event, Infusion-related Reactions (IRRs), serious AEs, and abnormalities in lab parameters

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2021)

• Objective Response Rate (ORR) [ Time Frame: 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 ]
  Proportion of subject with best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
• Pharmacokinetic (PK) of ABL503 [ Time Frame: 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 ]
  Serum concentrations of ABL503 will be collected and analyzed to evaluate the PK of ABL503
• Immunogenicity of ABL503 [ Time Frame: 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 ]
  Incidence of anti-ABL503 antibody will be analyzed to evaluate the Immunogenicity of ABL503

• 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: 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
• 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
• Brief 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

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.

Study Arms

Experimental: ABL503

ABL503 will be administered biweekly of every 28-day cycle in the dose-escalation. 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.

Intervention: Drug: ABL503

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 23, 2023): 100
• Original Estimated Enrollment (submitted: February 17, 2021): 36
• Estimated Study Completion Date: June 15, 2025
• Estimated Primary Completion Date: June 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Juyeun Jeon; +82-31-8014-7039; juyeun.jeon@ablbio.com

• Listed Location Countries: Korea, Republic of, United States

Administrative Information

• NCT Number: NCT04762641
• Other Study ID Numbers: ABL503-1001
• Has Data Monitoring Committee: No

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

• Plan to Share IPD: No

• Current Responsible Party: ABL Bio, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ABL Bio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ABL Bio, Inc.
• Verification Date: August 2023