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

NCT ID: NCT04777994

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

248 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-09

Study Completion Date

2026-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Solid Tumor Cancer

Keywords

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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)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Monotherapy Dose Escalation

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

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

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

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

Programmed Cell Death-1 (PD-1) Inhibitor

Intervention Type DRUG

Intravenous (IV) infusion

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)

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

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.

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

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

Intervention Type DRUG

Oral Tablet

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

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

Programmed Cell Death-1 (PD-1) Inhibitor

Intervention Type DRUG

Intravenous (IV) infusion

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.

Group Type EXPERIMENTAL

ABBV-CLS-484

Intervention Type DRUG

Oral Capsule

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

Intervention Type DRUG

Oral Tablet

Interventions

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ABBV-CLS-484

Oral Capsule

Intervention Type DRUG

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

Oral Tablet

Intervention Type DRUG

Programmed Cell Death-1 (PD-1) Inhibitor

Intravenous (IV) infusion

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Calico Life Sciences LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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University of Arizona Cancer Center - Tucson /ID# 262698

Tucson, Arizona, United States

Site Status RECRUITING

Yale University School of Medicine /ID# 225707

New Haven, Connecticut, United States

Site Status RECRUITING

Johns Hopkins Hospital /ID# 254056

Baltimore, Maryland, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center /ID# 252009

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute /ID# 249642

Boston, Massachusetts, United States

Site Status RECRUITING

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

Ann Arbor, Michigan, United States

Site Status RECRUITING

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

New York, New York, United States

Site Status RECRUITING

Duke Cancer Center /ID# 251975

Durham, North Carolina, United States

Site Status RECRUITING

Carolina BioOncology Institute /ID# 225704

Huntersville, North Carolina, United States

Site Status COMPLETED

Perelman Center for Advanced Medicine /ID# 250188

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UPMC Hillman Cancer Ctr /ID# 225706

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705

Providence, Rhode Island, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center /ID# 251974

Dallas, Texas, United States

Site Status RECRUITING

University of Texas MD Anderson Cancer Center /ID# 252004

Houston, Texas, United States

Site Status RECRUITING

NEXT Oncology /ID# 225708

San Antonio, Texas, United States

Site Status COMPLETED

Institut Paoli-Calmettes /ID# 260956

Marseille, Bouches-du-Rhone, France

Site Status RECRUITING

IUCT Oncopole /ID# 252673

Toulouse, Occitanie, France

Site Status RECRUITING

Centre Antoine-Lacassagne /ID# 252606

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

Site Status RECRUITING

Hopital Foch /ID# 252607

Suresnes, , France

Site Status RECRUITING

Rabin Medical Center /ID# 263631

Petah Tikva, Central District, Israel

Site Status RECRUITING

Hadassah Medical Center /ID# 252366

Jerusalem, Jerusalem, Israel

Site Status RECRUITING

The Chaim Sheba Medical Center /ID# 226756

Ramat Gan, Tel Aviv, Israel

Site Status RECRUITING

National Cancer Center Hospital /ID# 225884

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Wakayama Medical University Hospital /ID# 252988

Wakayama, Wakayama, Japan

Site Status RECRUITING

Seoul National University Hospital /ID# 254635

Seoul, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Samsung Medical Center /ID# 260664

Seoul, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Yonsei University Health System Severance Hospital /ID# 260665

Seoul, , South Korea

Site Status RECRUITING

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

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre /ID# 257374

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario HM Sanchinarro /ID# 228034

Madrid, Madrid, Spain

Site Status RECRUITING

Countries

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United States France Israel Japan South Korea Spain

Central Contacts

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ABBVIE CALL CENTER

Role: CONTACT

Phone: 844-663-3742

Email: [email protected]

Facility Contacts

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Site Coordinator

Role: primary

Site Coordinator

Role: primary

Site Coordinator

Role: primary

Site Coordinator

Role: primary

Site Coordinator

Role: primary

References

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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.

Reference Type DERIVED
PMID: 37794185 (View on PubMed)

Related Links

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Other Identifiers

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2023-507568-38-00

Identifier Type: OTHER

Identifier Source: secondary_id

M20-431

Identifier Type: -

Identifier Source: org_study_id