A Phase 1 Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors
Summary
The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-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 ABBV-CLS-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.
Arms & interventions
- DrugABBV-CLS-484
Oral Capsule
- DrugVascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Oral Tablet
- DrugProgrammed Cell Death-1 (PD-1) Inhibitor
Intravenous (IV) infusion
Outcome measures
Primary
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
Secondary
Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy)
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)
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)
Time frame: Baseline through Study Completion (approximately 3 years)
Eligibility criteria
Study locations (15)
University of Arizona Cancer Center - Tucson /ID# 262698
Tucson, Arizona, 85724
Yale University School of Medicine /ID# 225707
New Haven, Connecticut, 06510
Johns Hopkins Hospital /ID# 254056
Baltimore, Maryland, 21287
Beth Israel Deaconess Medical Center /ID# 252009
Boston, Massachusetts, 02215-5400
Dana-Farber Cancer Institute /ID# 249642
Boston, Massachusetts, 02215
University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
Ann Arbor, Michigan, 48109
NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
New York, New York, 10016
Duke Cancer Center /ID# 251975
Durham, North Carolina, 27710
Carolina BioOncology Institute /ID# 225704
Huntersville, North Carolina, 28078
Perelman Center for Advanced Medicine /ID# 250188
Philadelphia, Pennsylvania, 19104
UPMC Hillman Cancer Ctr /ID# 225706
Pittsburgh, Pennsylvania, 15232
Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705
Providence, Rhode Island, 02903-4923
University of Texas Southwestern Medical Center /ID# 251974
Dallas, Texas, 75390-7208
University of Texas MD Anderson Cancer Center /ID# 252004
Houston, Texas, 77030
NEXT Oncology /ID# 225708
San Antonio, Texas, 78229
References
- Baumgartner CK, Ebrahimi-Nik H, Iracheta-Vellve A, Hamel KM, Olander KE, Davis TGR, McGuire KA, Halvorsen GT, Avila OI, Patel CH, Kim SY, Kammula AV, Muscato AJ, Halliwill K, Geda P, Klinge KL, Xiong Z, Duggan R, Mu L, Yeary MD, Patti JC, Balon TM, Mathew R, Backus C, Kennedy DE, Chen A, Longenecker K, Klahn JT, Hrusch CL, Krishnan N, Hutchins CW, Dunning JP, Bulic M, Tiwari P, Colvin KJ, Chuong CL, Kohnle IC, Rees MG, Boghossian A, Ronan M, Roth JA, Wu MJ, Suermondt JSMT, Knudsen NH, Cheruiyot CK, Sen DR, Griffin GK, Golub TR, El-Bardeesy N, Decker JH, Yang Y, Guffroy M, Fossey S, Trusk P, Sun IM, Liu Y, Qiu W, Sun Q, Paddock MN, Farney EP, Matulenko MA, Beauregard C, Frost JM, Yates KB, Kym PR, Manguso RT. The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature. 2023 Oct;622(7984):850-862. doi: 10.1038/s41586-023-06575-7. Epub 2023 Oct 4.(PubMed)