A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-579 Alone and in Combination With Anti-PD-1 in Subjects With Locally Advanced or Metastatic Tumors

Primary Outcome Measures  :

1. Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]Maximum plasma/serum concentration of ABBV-CLS-579
   
2. Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4 Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]Maximum plasma/serum concentration of Metabolite M4
   
3. Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]Maximum plasma/serum concentration of PD-1 inhibitor
   
4. Time To Cmax (Tmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]The amount of time taken to reach Cmax
   
5. Time To Cmax (Tmax) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]The amount of time taken to reach Cmax
   
6. Time To Cmax (Tmax) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]The amount of time taken to reach Cmax
   
7. Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]Terminal phase elimination rate constant (β or Beta)
   
8. Terminal Phase Elimination Rate Constant (β) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]Terminal phase elimination rate constant (β or Beta)
   
9. Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]Terminal phase elimination rate constant (β or Beta)
   
10. Terminal Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]Terminal phase elimination half-life (t1/2)
    
11. Terminal Phase Elimination Rate Half-Life (t1/2) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]Terminal phase elimination half-life (t1/2)
    
12. Terminal Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]Terminal phase elimination half-life (t1/2)
    
13. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
    
14. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
    
15. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
    
16. Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-579 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]The MTD and/or RP2D of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study
    
17. Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor [ Time Frame: Baseline through Study Completion (approximately 3 years) ]The MTD and/or RP2D of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study

Inclusion Criteria:

• Must weigh at least 35 kilograms (kg).
• Histologically or cytologically proven metastatic or locally advanced tumors (with measurable disease defined by Response Evaluation Criteria In Solid Tumors [RECIST] v1.1), for which no effective standard therapy exists, or where standard therapy has failed. Participants must have received at least 1 prior anticancer therapy for the indication being considered.
• 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 < 450 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.

Exclusion Criteria:

• Untreated brain or meningeal metastases (participants 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.
• 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, cardiac arrythmia or peripheral artery disease.
• 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 participation in this study or would make the participant an unsuitable candidate to receive study drug.
• History of uncontrolled, clinically significant endocrinopathy.
• Known gastrointestinal disorders making absorption of oral medications problematic. Inability to swallow capsules.
• If treated with anti-programmed cell death protein-1 (aPD-1)/antiprogrammed cell death protein-ligand 1(aPD-L1) targeting or other immunostimulatory 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 ≥ 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 practice.