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RecruitingInterventionalPhase 1

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

NCT ID: NCT04762641Sponsor: ABL Bio, Inc.Last updated: 2025-02-06

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

Arms & interventions

  • DrugABL503

    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.

Outcome measures

Primary

  • Number of Subjects with Dose-Limiting Toxicities (DLT)

    Number of subjects with Dose-Limiting Toxicity (DLT)

    Time frame: From Day 1 until disease progression or Day 28, whichever came first

  • 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

    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

Secondary

  • 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

  • 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

  • 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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (5)

City of Hope

Duarte, California, 91010

Recruiting
JuYeon Jeon · Contact

USC

Los Angeles, California, 90033

Recruiting
Juyeun Jeon · Contact

UCLA

Santa Monica, California, 90404

Recruiting
JuYeon Jeon · Contact

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

Recruiting
Juyeun Jeon · Contact

NEXT Oncology

San Antonio, Texas, 78229

Recruiting
Juyeun Jeon · Contact