Clinical trial NCT05101109: Study to Evaluate the Safety and Tolerability of ABL501, and to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ABL501 in Subjects With Any Progressive, Locally Advanced (Unresectable) or Metastatic Solid Tumors
Official title: A Phase 1 Dose Escalation and Expansion Study of ABL501, a Bispecific Antibody of PD-L1 and LAG-3 as a Single Agent in Subjects With Any Progressive, Locally Advanced (Unresectable) or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: LAG-3
PD-L1
Immune oncology
solid tumor
bispecific antibody
Lead sponsor: ABL Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Drug: ABL501
Primary purpose: TREATMENT

Brief summary: This is a first-in-human (FIH) phase 1 open-label, multicenter, multiple-dose, dose-escalation and dose-expansion study of ABL501 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, preliminary anti-tumor activity, and the PD effect of ABL501 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors. This study included 2 parts; a dose-escalation part and a dose expansion part.

Detailed description: This is consisted with dose-escalation and dose-expansion study of ABL501 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, anti-tumor activity, and the PD effect of ABL501 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors.

Eligibility criteria: Inclusion Criteria:

* Histologically and/or cytologically confirmed any progressive, locally advanced (unresectable), or metastatic solid tumors that have relapsed or are refractory following the last line of treatment and for which prior standard therapy has been ineffective, standard therapy does not exist, or is not considered appropriate.
* Subjects with adverse events(AEs) excluding alopecia or Grade 2 toxicities that are deemed stable or irreversible (e.g., 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 study drug.
* Subject with adequate hematologic, hepatic, and renal functions confirmed based on the screening laboratory test within 7 days prior to the first administration of ABL501

Exclusion Criteria:

* Subjects has received prior anticancer monoclonal antibody treatment or investigational therapy within 28 days prior to the first administration of ABL501 or who has recovered (i.e., =\<Grade 1 or at baseline grade) from AEs due to previously administered agent more than 14 days prior to ABL501 administration.
* Subject has had 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 (i.e., =\<Grade 1 or at baseline grade) from AEs due to previously administered agent more than 14 days prior to ABL501 administration
* Subject discontinued from prior immunomodulatory therapy due to any intolerable immune-related AE(s) (irAEs) requiring systemic steroid treatment.

Primary outcomes:
measure: Number of subjects with dose-limiting toxicities (DLT)
timeFrame: from Day 1 until Day 28
measure: Number of subjects who experience with TEAEs, SAEs, irAEs and IRRs
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
measure: Number of subjects who experience with treatment-related TEAEs, SAEs, irAEs and IRRs
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
measure: Number of subjects who experience with clinically significant changes in laboratory values
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
Secondary outcomes:
measure: Pharmacokinetic profile of ABL501
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
measure: Objective Response Rate (ORR)
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
measure: number of subject with anti-drug antibodies (ADAs)
timeFrame: From Day 1 until confirmed CR, disease progression, unacceptable toxicity or subject/investigator's decision to terminate the study participation, assessed up to 24 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Clinical development team
name: Sangmi Lee
role: STUDY_DIRECTOR
References:
citation: Sung E, Ko M, Won JY, Jo Y, Park E, Kim H, Choi E, Jung UJ, Jeon J, Kim Y, Ahn H, Choi DS, Choi S, Hong Y, Park H, Lee H, Son YG, Park K, Won J, Oh SJ, Lee S, Kim KP, Yoo C, Song HK, Jin HS, Jung J, Park Y. LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. Mol Ther. 2022 Aug 3;30(8):2800-2816. doi: 10.1016/j.ymthe.2022.05.003. Epub 2022 May 6.