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NCT04777994PHASE1Recruiting

Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors

Calico Life Sciences LLC

Start Date

3/9/2021

Completion Date

10/1/2026

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 Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

ABBV-CLS-484

DRUG

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

DRUG

Programmed Cell Death-1 (PD-1) Inhibitor

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Conditions

Advanced Solid Tumor Cancer

Locations

University of Arizona Cancer Center - Tucson /ID# 262698

Tucson, Arizona 85724

United States

Yale University School of Medicine /ID# 225707

New Haven, Connecticut 06510

United States

Johns Hopkins Hospital /ID# 254056

Baltimore, Maryland 21287

United States

Beth Israel Deaconess Medical Center /ID# 252009

Boston, Massachusetts 02215-5400

United States

Dana-Farber Cancer Institute /ID# 249642

Boston, Massachusetts 02215

United States

University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010

Ann Arbor, Michigan 48109

United States

NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869

New York, New York 10016

United States

Duke Cancer Center /ID# 251975

Durham, North Carolina 27710

United States

Carolina BioOncology Institute /ID# 225704

Huntersville, North Carolina 28078

United States

Perelman Center for Advanced Medicine /ID# 250188

Philadelphia, Pennsylvania 19104

United States

UPMC Hillman Cancer Ctr /ID# 225706

Pittsburgh, Pennsylvania 15232

United States

Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705

Providence, Rhode Island 02903-4923

United States

University of Texas Southwestern Medical Center /ID# 251974

Dallas, Texas 75390-7208

United States

University of Texas MD Anderson Cancer Center /ID# 252004

Houston, Texas 77030

United States

NEXT Oncology /ID# 225708

San Antonio, Texas 78229

United States

Institut Paoli-Calmettes /ID# 260956

Marseille, Bouches-du-Rhone 13009

France

IUCT Oncopole /ID# 252673

Toulouse, Occitanie 31059

France

Centre Antoine-Lacassagne /ID# 252606

Nice, Provence-Alpes-Côte d'Azur Region 06189

France

Hopital Foch /ID# 252607

Suresnes, 92151

France

Rabin Medical Center /ID# 263631

Petah Tikva, Central District 4941492

Israel

Hadassah Medical Center /ID# 252366

Jerusalem, Jerusalem 91120

Israel

The Chaim Sheba Medical Center /ID# 226756

Ramat Gan, Tel Aviv 5265601

Israel

National Cancer Center Hospital /ID# 225884

Chuo-ku, Tokyo 104-0045

Japan

Wakayama Medical University Hospital /ID# 252988

Wakayama, Wakayama 641-8510

Japan

Seoul National University Hospital /ID# 254635

Seoul, Seoul Teugbyeolsi 03080

South Korea

Samsung Medical Center /ID# 260664

Seoul, Seoul Teugbyeolsi 06351

South Korea

Yonsei University Health System Severance Hospital /ID# 260665

Seoul, 03722

South Korea

Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524

L'Hospitalet de Llobregat, Barcelona 08907

Spain

Hospital Universitario 12 de Octubre /ID# 257374

Madrid, Madrid 28041

Spain

Hospital Universitario HM Sanchinarro /ID# 228034

Madrid, Madrid 28050

Spain