Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors (NCT04777994) — USA Trial Details

Condition(s) studied

Advanced Solid Tumor Cancer

Investigational drug(s) / intervention(s)

ABBV-CLS-484Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)Programmed Cell Death-1 (PD-1) Inhibitor

ABBV-CLS-484: Oral Capsule

Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI): Oral Tablet

Programmed Cell Death-1 (PD-1) Inhibitor: Intravenous (IV) infusion

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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: * Participants with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Participants must have received at least 1 prior systemic anticancer therapy for the indication being considered. For Monotherapy Dose Expansion only: * Participants 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 * Participants no recent history of hemorrhage, including hemoptysis, hematemesis, or melena * Participants 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.

Primary outcome measure(s)

Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) — Baseline Up to Approximately Day 42
Maximum plasma/serum concentration of ABBV-CLS-484
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy) — Baseline Up to Approximately Day 64
Maximum plasma/serum concentration of PD-1 inhibitor
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFRTKI (Combination therapy) Maximum plasma/serum concentration of PD-1 inhibitor — Baseline Up to Approximately Day 64
Maximum plasma/serum concentration of PD-1 inhibitor
Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) — Baseline Up to Approximately Day 42
The amount of time taken to reach Cmax
Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) — Baseline Up to Approximately Day 64
The amount of time taken to reach Cmax
Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy) — Baseline Up to Approximately Day 64
The amount of time taken to reach Cmax
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) — Baseline Up to Approximately Day 42
Terminal phase elimination half-life (t1/2)
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) — Baseline Up to Approximately Day 64
Terminal phase elimination half-life (t1/2)
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy) — Baseline Up to Approximately Day 64
Terminal phase elimination half-life (t1/2)
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy) — Baseline Up to Approximately Day 42
AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy) — 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
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy) — 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
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 — Baseline Up to Approximately Day 42
The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy therapy dose escalation phase of the study
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy) — Baseline Up to Approximately Day 64
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
Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy) — Baseline Up to Approximately Day 64
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
Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy) — Baseline Up to Approximately Day 42
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
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) — Baseline Up to Approximately Day 64
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
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) — Baseline Up to Approximately Day 64
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment

Trial sites (30)

Facility	City	Region	Status
University of Arizona Cancer Center - Tucson /ID# 262698	Tucson	Arizona	Recruiting
Yale University School of Medicine /ID# 225707	New Haven	Connecticut	Recruiting
Johns Hopkins Hospital /ID# 254056	Baltimore	Maryland	Recruiting
Beth Israel Deaconess Medical Center /ID# 252009	Boston	Massachusetts	Recruiting
Dana-Farber Cancer Institute /ID# 249642	Boston	Massachusetts	Recruiting
University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010	Ann Arbor	Michigan	Recruiting
NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869	New York	New York	Recruiting
Duke Cancer Center /ID# 251975	Durham	North Carolina	Recruiting
Carolina BioOncology Institute /ID# 225704	Huntersville	North Carolina	Completed
Perelman Center for Advanced Medicine /ID# 250188	Philadelphia	Pennsylvania	Recruiting
UPMC Hillman Cancer Ctr /ID# 225706	Pittsburgh	Pennsylvania	Recruiting
Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705	Providence	Rhode Island	Recruiting
University of Texas Southwestern Medical Center /ID# 251974	Dallas	Texas	Recruiting
University of Texas MD Anderson Cancer Center /ID# 252004	Houston	Texas	Recruiting
NEXT Oncology /ID# 225708	San Antonio	Texas	Completed
Institut Paoli-Calmettes /ID# 260956	Marseille	Bouches-du-Rhone	Recruiting
IUCT Oncopole /ID# 252673	Toulouse	Occitanie	Recruiting
Centre Antoine-Lacassagne /ID# 252606	Nice	Provence-Alpes-Côte d'Azur Region	Recruiting
Hopital Foch /ID# 252607	Suresnes	France	Recruiting
Rabin Medical Center /ID# 263631	Petah Tikva	Central District	Recruiting
Hadassah Medical Center /ID# 252366	Jerusalem	Jerusalem	Recruiting
The Chaim Sheba Medical Center /ID# 226756	Ramat Gan	Tel Aviv	Recruiting
National Cancer Center Hospital /ID# 225884	Chuo-ku	Tokyo	Recruiting
Wakayama Medical University Hospital /ID# 252988	Wakayama	Wakayama	Recruiting
Seoul National University Hospital /ID# 254635	Seoul	Seoul Teugbyeolsi	Recruiting
Samsung Medical Center /ID# 260664	Seoul	Seoul Teugbyeolsi	Recruiting
Yonsei University Health System Severance Hospital /ID# 260665	Seoul	South Korea	Recruiting
Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524	L'Hospitalet de Llobregat	Barcelona	Recruiting
Hospital Universitario 12 de Octubre /ID# 257374	Madrid	Madrid	Recruiting
Hospital Universitario HM Sanchinarro /ID# 228034	Madrid	Madrid	Recruiting

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