A Phase I, Multi-center, Open Label First-in-Human Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

Study Identifier:
M20-431
CT.gov Identifier:
NCT04777994
EudraCT Identifier:
202351000000
EU Trial (CTIS) Number:
2023-507568-38-00
Study Contact Information:
N/A
Recruiting

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Study Summary

To  assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Monotherapy Dose Escalation
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  • Drug: Intervention:
  • Drug: Experimental: Combination Dose Escalation with PD-1 Inhibitor
  • Drug: Drug: Programmed Cell Death-1 (PD-1) Inhibitor
  • Drug: Drug: ABBV-CLS-484
  • Drug: Experimental: Combination Dose Escalation with VEGFR TKI
  • Drug: Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
  • Drug: Experimental: Combination Expansion
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Must weigh at least 35 kilograms (kg).
    • An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
    • Life expectancy of ≥ 12 weeks.
    • Laboratory values meeting protocol criteria.
    • QT interval corrected for heart rate < 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
    • Measurable disease defined by RECIST 1.1 criteria.
    • For Monotherapy and Combination Dose Escalation:
    • • Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.
    • For Monotherapy Dose Expansion only:
    • Subjects must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
    • Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
    • Relapsed/refractory HNSCC
    • Relapsed/refractory NSCLC
    • Advanced ccRCC
    • For PD-1 Targeting Agent Combination Dose Expansion only:
    • For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
    • Relapsed HNSCC
    • Relapsed NSCLC
    • Relapsed Advanced ccRCC
    • For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
    • Locally Advanced or metastatic MSI-H tumors
    • For VEGFR TKI Combination Dose Expansion only:
    • Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
    • Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
    • Subjects with poorly controlled hypertension are excluded
    Exclusion criteria
    • Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
    • Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
    • Unresolved Grade 2 or higher peripheral neuropathy.
    • History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
    • Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
    • Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
    • History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
    • History of uncontrolled, clinically significant endocrinopathy.
    • Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
    • If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
    • Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
    • History of solid organ transplant or allogeneic stem cell transplant.
    • History of other malignancy, with the following exceptions:
    • No known active disease present for > or = 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
    • Adequately treated carcinoma in situ without evidence of disease.
    • History of interstitial lung disease or pneumonitis.
    • Major surgery < or = 28 days prior to first dose of study drug
    • Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor