Advanced Solid Tumor
Conditions
Interventions
Monotherapy Dose Escalation
ABBV-CLS-484 will be administered as a monotherapy in subjects with advanced solid tumors.
Combination Dose Escalation
ABBV-CLS-484 will be administered together with pemb
Sponsors
Sakanishi Ryuichi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult subjects weighing at least 35 kg who meet the following key eligibility criteria will be enrolled: 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. Specific criteria are required depending on enrollment cohort. For Monotherapy HNSCC Dose Expansion only: Subjects with relapsed/refractory HNSCC who have received 1-3 prior lines of therapy (and no more than 1 prior line containing PD-1/PD-L1 targeted therapy) whose tumors express PD-L1 (combined positive score [CPS] >= 1) as determined by the Food and Drug Administration (FDA)-approved PD-L1 immunohistochemistry (IHC) assays.a For Monotherapy and Pembrolizumab Combination ccRCC Dose Expansions only: Subjects with advanced ccRCC who must have been previously treated with at least 1 prior line of therapy (and no more than 1 prior line containing PD-1/PD-L1 targeted therapy) in the locally advanced or metastatic setting. For Pembrolizumab Combination NSCLC and MSI-H Dose Expansion only: For the following tumor types, subjects must have received at least 1 prior line of therapy (and no more than 1 prior line containing PD-1/PD-L1 targeted therapy): -NSCLC(outcome of prior PD-1/PD-L1 targeted therapy: relapsed), tumors express PD-L1 (TPS>=1%)a -NSCLC(outcome of prior PD-1/PD-L1 targeted therapy: refractory), tumors express PD-L1 (TPS>=1%)a -MSI-H tumors(outcome of prior PD-1/PD-L1 targeted therapy: refractory), Locally advanced or metastatic MSI-H tumors whose tumors are determined to have a MSI-H status by PCR or NGS tests, or dMMR by IHC tests. a. Prior PD-L1 test results per Agilent PD-L1 22C3 (preferred), Ventana PD-L1 SP142, Ventana SP263 or Dako 28-8 IHC assays are acceptable. PD-L1 positivity must be determined prior to enrollment. If PD-L1 IHC assay results are not available, the subjects tumor tissue samples must be tested at designated local or sponsor approved central lab for PD-L1 status prior to enrollment. Note: Relapsed from prior PD-1/PD-L1 therapy is defined as the subject having received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months) Refractory to PD-1/PD-L1 therapy is defined as having received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression (in the absence of best response of CR/PR/stable disease by RECIST v1.1) with PD-1/PD-L1 targeted therapy. For Cabozantinib Combination Dose Expansion only: -Subjects with locally advanced or metastatic, advanced ccRCC who have relapsed after no more than 1 prior VEGFR TKI therapy with a best response of CR/PR/stable disease by RECIST v1.1. -Subjects with no recent history of hemorrhage, including hemoptysis, hematemesis, or melena. -Subjects must not have discontinued cabozantinib due to related toxicity when administered as monotherapy or in combination in previous line(s) of treatment. -Subjects with known hypersensitivity reaction to active ingredients or other ingredients of cabozantinib are excluded. -Subjects with known hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption (since cabozantinib formulation contains lactose) a
Exclusion criteria
Exclusion criteria: Subject must not have known gastrointestinal disorders making absorption of oral medications problematic. If treated with anti-PD-1/anti-PD-L1 targeting or other immunostimulatory agents in the past: excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, Grade 3 or higher hypersensitivity to administered drug or drug related toxicity requiring discontinuation. Exceptions to this exclusion criterion include the following: -Patients with a history of immune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. -Patients with immune-related controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. -Patients with immune-related controlled adrenal insufficiency on stable doses of hormone replacement may be eligible -Patients with immune-related controlled hypophysitis on stable doses of hormone replacement may be eligible. Subject must not have an active autoimmune disease requiring systemic immunosuppressive treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions). Subject must not have history of solid organ transplant or allogeneic stem cell transplant. Subject must not have history of or ongoing interstitial lung disease or pneumonitis. Subject must not have had major surgery <= 28 days prior to first dose of study drug. No history of other malignancy, with the following exceptions: -No known active disease present within 3 years before first dose of study treatment. For subjects with history of other malignancy beyond 3 years, must be felt to be at low risk of 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. No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices. Must not have been treated with any investigational drug or systemic anticancer treatments within 28 days or 5 half-lives of the drug (whichever is shorter) before the first dose of study drug or is currently enrolled in another clinical study. Must not have been previously treated with PTPN2/N1 inhibitors. Must not have been treated with steroids as anticancer therapy within 7 days before the first dose of study drug. Must not have systemically used known OAT3 inhibitors or MATE1/2-K inhibitors within 7 days before the first dose of study drug and throughout the first cycle. Must not have systemically used medications known to prolong the QT interval for at least 5 half-lives of the medication or 14 days (whichever is shorter) before the first dose of study drug and throughout Cycle 1. Must not have received any live vaccine within 28 days before the first dose of study drug or be expected to need a live vaccination during study participation including at least 28 days after the last dose of study drug. Must not have used immunosuppressive medications within 14 days of first dose of study drug. Physiologic doses of corticosteroids allowed. Palliative radiation or palliative surgery will be allowed if the subject is otherwise stable.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Efficacy Endpoint (Dose Expansion Portion only) Confirmed CR/PR by RECIST 1.1 Safety Endpoints The safety evaluation will be based on the assessment of AEs, laboratory parameters, vital signs, physical examination results and electrocardiogram (ECG) results. Pharmacokinetic Endpoints The following PK parameters for ABBV-CLS-484 may be estimated, as data allow: -Maximum observed plasma or serum concentration (Cmax) and the time to Cmax (Tmax), the terminal phase elimination half-life (t1/2), and area under the plasma or serum concentration time curve (AUC). - Additional parameters may be calculated, and analyses may be conducted if useful in the interpretation of the data. -Exploratory analysis of potential metabolites of ABBV-CLS-484 may be conducted with the PK samples collected for ABBV-CLS-484. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoint (Dose Escalation Portion only) Confirmed CR/PR by RECIST 1.1 | — |
Countries
France, Israel, Japan, South Korea, Spain, United States
Contacts
Public ContactRyuichi Sakanishi
PPD-SNBL K. K.
Outcome results
None listed