Recruiting
Phase 1

ABBV-CLS-484

Sponsor:

Calico Life Sciences LLC

Code:

NCT04777994

Conditions

Advanced Solid Tumor Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ABBV-CLS-484

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

Programmed Cell Death-1 (PD-1) Inhibitor

Study Details

Brief 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.

Conditions

Advanced Solid Tumor Cancer

Study ID

NCT04777994

Start date

Mar 9, 2021

Status verified date

Dec, 2025

Completion date

Oct, 2026

Anticipated

Primary completion date

Oct, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

248 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Monotherapy Dose Escalation

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

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

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)

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.

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

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.

Interventions

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

Primary outcome measure

  • Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  • Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy) [ Time Frame: 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 [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  • Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  • Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  • Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  • Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline Up to Approximately Day 64 ]

Central Contacts and Locations

Central contacts

Nicole Director Clinical Operations

650-754-6200info@calicolabs.com

Locations

University of Arizona Cancer Center - Tucson /ID# 262698

Recruiting

Tucson, Arizona, United States, 85724

Yale University School of Medicine /ID# 225707

Recruiting

New Haven, Connecticut, United States, 06510

Johns Hopkins Hospital /ID# 254056

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Coordinator

443-287-8312

Beth Israel Deaconess Medical Center /ID# 252009

Recruiting

Boston, Massachusetts, United States, 02215-5400

Dana-Farber Cancer Institute /ID# 249642

Recruiting

Boston, Massachusetts, United States, 02215

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

Recruiting

Ann Arbor, Michigan, United States, 48109

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

Recruiting

New York, New York, United States, 10016

Contacts

Site Coordinator

(212)-731-6230

Duke Cancer Center /ID# 251975

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Coordinator

(919) 681-7460

Perelman Center for Advanced Medicine /ID# 250188

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Site Coordinator

(215) 316-5151

UPMC Hillman Cancer Ctr /ID# 225706

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705

Recruiting

Providence, Rhode Island, United States, 02903-4923

University of Texas Southwestern Medical Center /ID# 251974

Recruiting

Dallas, Texas, United States, 75390-7208

University of Texas MD Anderson Cancer Center /ID# 252004

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Coordinator

713-792-2121

More Information

Sponsor

Calico Life Sciences LLC

Last update posted

Jun 4, 2026

Last verified

Dec, 2025

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)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Calico Life Sciences LLC on 2026-06-04.