The study will assess the safety, PK, PD, and preliminary efficacy of ABBVCLS-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). The trial aims to establish a safe, tolerable, and efficacious dose of ABBVCLS-484 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 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy 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 also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
248
Oral Capsule
Intravenous (IV) infusion
University of Arizona Cancer Center - Tucson /ID# 262698
Tucson, Arizona, United States
RECRUITINGYale University School of Medicine /ID# 225707
New Haven, Connecticut, United States
RECRUITINGJohns Hopkins Hospital /ID# 254056
Baltimore, Maryland, United States
RECRUITINGBeth Israel Deaconess Medical Center /ID# 252009
Boston, Massachusetts, United States
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
Maximum plasma/serum concentration of ABBV-CLS-484
Time frame: Baseline Up to Approximately Day 42
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy)
Maximum plasma/serum concentration of PD-1 inhibitor
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFRTKI (Combination therapy) Maximum plasma/serum concentration of PD-1 inhibitor
Maximum plasma/serum concentration of PD-1 inhibitor
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 42
Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 64
Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)
The amount of time taken to reach Cmax
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 42
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
Terminal phase elimination half-life (t1/2)
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy)
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 42
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)
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
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy)
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
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484
The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy therapy dose escalation phase of the study
Time frame: Baseline Up to Approximately Day 42
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)
The MTD and/or RP2D of ABBV-CLS-484 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy)
The MTD and/or RP2D of ABBV-CLS-484 and VEGFR TKI will be determined during the combination therapy dose escalation phase of the study
Time frame: Baseline Up to Approximately Day 64
Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline Up to Approximately Day 42
Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Time frame: Baseline Up to Approximately Day 64
Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy)
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)
Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
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)
Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
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)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Dana-Farber Cancer Institute /ID# 249642
Boston, Massachusetts, United States
RECRUITINGUniversity of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
Ann Arbor, Michigan, United States
RECRUITINGNYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
New York, New York, United States
RECRUITINGDuke Cancer Center /ID# 251975
Durham, North Carolina, United States
RECRUITINGCarolina BioOncology Institute /ID# 225704
Huntersville, North Carolina, United States
COMPLETEDPerelman Center for Advanced Medicine /ID# 250188
Philadelphia, Pennsylvania, United States
RECRUITING...and 20 more locations