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

NCT04777994 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: M20-4312023-507568-38-00
• Study Type: interventional
• Target: 248
• Locations: 6 countries
• Sites: 30

Brief Summary

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.

Conditions

Advanced Solid Tumor Cancer

Keywords

Cancer; Tumor; anti-PD-1; ABBV-CLS-484; clear cell renal cell carcinoma (ccRCC); head and neck squamous cell carcinoma (HNSCC); non-small cell lung cancer (NSCLC); relapsed or refractory (R/R); Microsatellite instability - high tumors (MSI-H); Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)

Outcome Measures

Primary Outcomes (18)

• Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)

  Maximum plasma/serum concentration of ABBV-CLS-484

  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

  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

  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

  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

  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

  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)

  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)

  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)

  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

  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

  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

  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

  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

  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

  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

  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

  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

  Baseline Up to Approximately Day 64

Secondary Outcomes (3)

• Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy)

  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)

  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)

  Baseline through Study Completion (approximately 3 years)

Study Arms (6)

Monotherapy Dose Escalation

EXPERIMENTAL

ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors

Drug: ABBV-CLS-484

Combination Dose Escalation with PD-1 Inhibitor

EXPERIMENTAL

ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor

Monotherapy Expansion

EXPERIMENTAL

ABBV-CLS-484 will be administered 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)

Drug: ABBV-CLS-484

Combination Expansion with PD-1 Inhibitor

EXPERIMENTAL

ABBV-CLS-484 will be administered at the determined recommended dose in combination with Programmed Cell Death-1 Inhibitor in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.

Drug: ABBV-CLS-484; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)

Combination Dose Escalation with VEGFR TKI

EXPERIMENTAL

ABBV-CLS-484 will be administered in combination with a Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) in subjects with solid tumors

Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor

Combination Expansion

EXPERIMENTAL

ABBV-CLS-484 will be administered at the determined recommended dose in combination with VEGFR TKI in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.

Drug: ABBV-CLS-484; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)

Interventions

ABBV-CLS-484 DRUG

Oral Capsule

Combination Dose Escalation with PD-1 Inhibitor; Combination Dose Escalation with VEGFR TKI; Combination Expansion; Combination Expansion with PD-1 Inhibitor; Monotherapy Dose Escalation; Monotherapy Expansion

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

Oral Tablet

Combination Expansion; Combination Expansion with PD-1 Inhibitor

Programmed Cell Death-1 (PD-1) Inhibitor DRUG

Intravenous (IV) infusion

Combination Dose Escalation with PD-1 Inhibitor; Combination Dose Escalation with VEGFR TKI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Calico Life Sciences LLC: lead

Study Sites (30)

University of Arizona Cancer Center - Tucson /ID# 262698

Tucson, Arizona, 85724, United States

RECRUITING

Yale University School of Medicine /ID# 225707

New Haven, Connecticut, 06510, United States

RECRUITING

Johns Hopkins Hospital /ID# 254056

Baltimore, Maryland, 21287, United States

RECRUITING

Beth Israel Deaconess Medical Center /ID# 252009

Boston, Massachusetts, 02215-5400, United States

RECRUITING

Dana-Farber Cancer Institute /ID# 249642

Boston, Massachusetts, 02215, United States

RECRUITING

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

Ann Arbor, Michigan, 48109, United States

RECRUITING

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

New York, New York, 10016, United States

RECRUITING

Duke Cancer Center /ID# 251975

Durham, North Carolina, 27710, United States

RECRUITING

Carolina BioOncology Institute /ID# 225704

Huntersville, North Carolina, 28078, United States

COMPLETED

Perelman Center for Advanced Medicine /ID# 250188

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UPMC Hillman Cancer Ctr /ID# 225706

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705

Providence, Rhode Island, 02903-4923, United States

RECRUITING

University of Texas Southwestern Medical Center /ID# 251974

Dallas, Texas, 75390-7208, United States

RECRUITING

University of Texas MD Anderson Cancer Center /ID# 252004

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology /ID# 225708

San Antonio, Texas, 78229, United States

COMPLETED

Institut Paoli-Calmettes /ID# 260956

Marseille, Bouches-du-Rhone, 13009, France

RECRUITING

IUCT Oncopole /ID# 252673

Toulouse, Occitanie, 31059, France

RECRUITING

Centre Antoine-Lacassagne /ID# 252606

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

RECRUITING

Hopital Foch /ID# 252607

Suresnes, 92151, France

RECRUITING

Rabin Medical Center /ID# 263631

Petah Tikva, Central District, 4941492, Israel

RECRUITING

Hadassah Medical Center /ID# 252366

Jerusalem, Jerusalem, 91120, Israel

RECRUITING

The Chaim Sheba Medical Center /ID# 226756

Ramat Gan, Tel Aviv, 5265601, Israel

RECRUITING

National Cancer Center Hospital /ID# 225884

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Wakayama Medical University Hospital /ID# 252988

Wakayama, Wakayama, 641-8510, Japan

RECRUITING

Seoul National University Hospital /ID# 254635

Seoul, Seoul Teugbyeolsi, 03080, South Korea

RECRUITING

Samsung Medical Center /ID# 260664

Seoul, Seoul Teugbyeolsi, 06351, South Korea

RECRUITING

Yonsei University Health System Severance Hospital /ID# 260665

Seoul, 03722, South Korea

RECRUITING

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

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Hospital Universitario 12 de Octubre /ID# 257374

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Universitario HM Sanchinarro /ID# 228034

Madrid, Madrid, 28050, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 37794185 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms; Carcinoma, Renal Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

osunprotafib; Receptors, Vascular Endothelial Growth Factor; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Receptor Protein-Tyrosine Kinases; Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Cell Surface; Membrane Proteins; Receptors, Growth Factor; Receptors, Peptide; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 2, 2021
• Study Start: March 9, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); FR (4); KR (3); JP (2); IL (3); ES (3)