The purpose of this study is to see how safe and effective ABBV-CLS-579 is when used alone and in combination with a PD-1 target agent or with a VEGF TKI. ABBV-CLS-579 is an investigational drug being developed for the treatment of tumors. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-579 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation, and Part 3 Combination Dose Expansion. Part 1, ABBV-CLS-579 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-579 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-579 will be administered at the determined recommended dose in combination with a PD-1 target agent or with a VEGFR TKI 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). Adult participants with a diagnosis of some solid tumors for which no effective standard therapy exists or has failed will be enrolled. Participants will receive study treatment until disease progresses or discontinued. There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects, and completing questionnaires.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
101
Highlands Oncology Group Springdale
Springdale, Arkansas, United States
Yale University
New Haven, Connecticut, United States
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States
Carolina BioOncology Institute
Huntersville, North Carolina, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Hopital Saint-Andre
Bordeaux, France
Institut Gustave Roussy
Villejuif, France
The Chaim Sheba Medical Center
Ramat Gan, Israel
National Cancer Center Hospital East
Kashiwa-Shi, Chiba, Japan
Wakayama Medical University Hospital
Wakayama, Wakayama, Japan
...and 7 more locations
Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579
Maximum plasma/serum concentration of ABBV-CLS-579
Time frame: Baseline Up to Approximately Day 44
Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4
Maximum plasma/serum concentration of Metabolite M4
Time frame: Baseline Up to Approximately Day 44
Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor
Maximum plasma/serum concentration of PD-1 inhibitor
Time frame: Baseline Up to Approximately Day 64
Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI
Maximum plasma/serum concentration of VEGFR TKI
Time frame: Baseline Up to Approximately Day 64
Time To Cmax (Tmax) Of ABBV-CLS-579
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 44
Time To Cmax (Tmax) Of Metabolite M4
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 44
Time To Cmax (Tmax) Of PD-1 Inhibitor
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 64
Time To Cmax (Tmax) Of VEGFR TKI
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 64
Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579
Terminal phase elimination rate constant (β or Beta)
Time frame: Baseline Up to Approximately Day 44
Terminal Phase Elimination Rate Constant (β) Of Metabolite M4
Terminal phase elimination rate constant (β or Beta)
Time frame: Baseline Up to Approximately Day 44
Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor
Terminal phase elimination rate constant (β or Beta)
Time frame: Baseline Up to Approximately Day 64
Terminal Phase Elimination Rate Constant (β) Of VEGFR TKI
Terminal phase elimination rate constant (β or Beta)
Time frame: Baseline Up to Approximately Day 64
Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 44
Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 44
Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 64
Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 64
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579
AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
Time frame: Baseline Up to Approximately Day 44
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4
AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
Time frame: Baseline Up to Approximately Day 44
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor
AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
Time frame: Baseline Up to Approximately Day 64
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI
AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
Time frame: Baseline Up to Approximately Day 64
Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579
The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study
Time frame: Baseline through Study Completion (approximately 3 years)
Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor
The Expansion Dose and/or MTD of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
Time frame: Baseline through Study Completion (approximately 3 years)
Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline through Study Completion (approximately 3 years)
Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline through Study Completion (approximately 3 years)
Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline through Study Completion (approximately 3 years)
Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline through Study Completion (approximately 3 years)
Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1
BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
Time frame: Baseline through Study Completion (approximately 3 years)
Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1
BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
Time frame: Baseline through Study Completion (approximately 3 years)
Change from Baseline QTc
QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline
Time frame: Baseline through Study Completion (approximately 3 years)
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