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

A Phase 1 Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

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 Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor Cancer
• Intervention / Treatment: Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)

• Study Type: Interventional
• Enrollment (Estimated): 248
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• France
  • Suresnes, France, 92151
    • Recruiting
    • Hopital Foch /ID# 252607
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13009
      • Recruiting
      • Institut Paoli-Calmettes /ID# 260956
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • Recruiting
      • IUCT Oncopole /ID# 252673
  • Provence-Alpes-Côte d'Azur Region
    • Nice, Provence-Alpes-Côte d'Azur Region, France, 06189
      • Recruiting
      • Centre Antoine-Lacassagne /ID# 252606
• Israel
  • Central District
    • Petah Tikva, Central District, Israel, 4941492
      • Recruiting
      • Rabin Medical Center /ID# 263631
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Recruiting
      • Hadassah Medical Center /ID# 252366
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 226756
• Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital /ID# 225884
  • Wakayama
    • Wakayama, Wakayama, Japan, 641-8510
      • Recruiting
      • Wakayama Medical University Hospital /ID# 252988
• South Korea
  • Seoul, South Korea, 03722
    • Recruiting
    • Yonsei University Health System Severance Hospital /ID# 260665
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital /ID# 254635
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Recruiting
      • Samsung Medical Center /ID# 260664
• Spain
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Recruiting
      • Hospital Universitario 12 de Octubre /ID# 257374
    • Madrid, Madrid, Spain, 28050
      • Recruiting
      • Hospital Universitario HM Sanchinarro /ID# 228034
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona Cancer Center - Tucson /ID# 262698
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School of Medicine /ID# 225707
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital /ID# 254056
      • Contact: Site Coordinator; Phone Number: 443-287-8312
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Recruiting
      • Beth Israel Deaconess Medical Center /ID# 252009
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute /ID# 249642
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
      • Contact: Site Coordinator; Phone Number: (212)-731-6230
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Center /ID# 251975
      • Contact: Site Coordinator; Phone Number: (919) 681-7460
    • Huntersville, North Carolina, United States, 28078
      • Completed
      • Carolina BioOncology Institute /ID# 225704
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Perelman Center for Advanced Medicine /ID# 250188
      • Contact: Site Coordinator; Phone Number: (215) 316-5151
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Ctr /ID# 225706
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Recruiting
      • Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • Recruiting
      • University of Texas Southwestern Medical Center /ID# 251974
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center /ID# 252004
      • Contact: Site Coordinator; Phone Number: 713-792-2121
    • San Antonio, Texas, United States, 78229
      • Completed
      • NEXT Oncology /ID# 225708

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation; ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors	Drug: ABBV-CLS-484; Oral Capsule
Experimental: Combination Dose Escalation with PD-1 Inhibitor; ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors	Drug: ABBV-CLS-484; Oral Capsule; Drug: Programmed Cell Death-1 (PD-1) Inhibitor; Intravenous (IV) infusion
Experimental: Monotherapy Expansion; 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; Oral Capsule
Experimental: Combination Expansion with PD-1 Inhibitor; 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; Oral Capsule; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI); Oral Tablet
Experimental: Combination Dose Escalation with VEGFR TKI; 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; Oral Capsule; Drug: Programmed Cell Death-1 (PD-1) Inhibitor; Intravenous (IV) infusion
Experimental: Combination Expansion; 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; Oral Capsule; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI); Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Baseline through Study Completion (approximately 3 years)

Collaborators and Investigators

• Sponsor: Calico Life Sciences LLC
• Collaborators: Calico Life Sciences LLC
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; head and neck squamous cell carcinoma (HNSCC); anti-PD-1; Tumor; non-small cell lung cancer (NSCLC); ABBV-CLS-484; clear cell renal cell carcinoma (ccRCC); relapsed or refractory (R/R); Microsatellite instability - high tumors (MSI-H); Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Recurrence; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Enzymes; Enzymes and Coenzymes; Receptors, Cell Surface; Membrane Proteins; Receptors, Peptide; Transferases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Intracellular Signaling Peptides and Proteins; Protein-Tyrosine Kinases; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Tyrosine Kinase Inhibitors; osunprotafib; Receptors, Vascular Endothelial Growth Factor
• Other Study ID Numbers: M20-431; 2023-507568-38-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes