A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
Advanced Solid Tumor Cancer
About this trial
This is an interventional treatment trial for Advanced Solid Tumor Cancer focused on measuring Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Eligibility Criteria
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 within ≥ 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 ≤ 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.
Sites / Locations
- Yale UniversityRecruiting
- Dana-Farber Cancer InstituteRecruiting
- Carolina BioOncology InstituteRecruiting
- UPMC Hillman Cancer CenterRecruiting
- Lifespan Cancer Institute at Rhode Island HospitalRecruiting
- Next OncologyRecruiting
- IUCT OncopoleRecruiting
- Hadassah Medical CenterRecruiting
- The Chaim Sheba Medical CenterRecruiting
- Wakayama Medical University HospitalRecruiting
- National Cancer Center HospitalRecruiting
- Hospital Universitario HM SanchinarroRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Monotherapy Dose Escalation
Combination Dose Escalation with PD-1 Inhibitor
Monotherapy Expansion
Combination Expansion with PD-1 Inhibitor
Combination Dose Escalation with VEGFR TKI
Combination Expansion
ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors
ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
ABBV-CLS-484 will be administered at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC)
ABBV-CLS-484 will be administered at the determined recommended dose in combination with Programmed Cell Death-1 Inhibitor in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
ABBV-CLS-484 will be administered in combination with a Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) in subjects with solid tumors
ABBV-CLS-484 will be administered at the determined recommended dose in combination with VEGFR TKI in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.