First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors

NCT04417465 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: M20-1242020-000639-28
• Study Type: interventional
• Target: 101
• Locations: 7 countries
• Sites: 17

Brief Summary

The purpose of this study is to see how safe and effective ABBV-CLS-579 is when used alone and in combination with a PD-1 target agent or with a VEGF TKI. ABBV-CLS-579 is an investigational drug being developed for the treatment of tumors. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-579 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 Combination Dose Expansion. Part 1, ABBV-CLS-579 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-579 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-579 will be administered at the determined recommended dose in combination with a PD-1 target agent or with a VEGFR TKI 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). Adult participants with a diagnosis of some solid tumors for which no effective standard therapy exists or has failed will be enrolled. Participants will receive study treatment until disease progresses or discontinued. There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects, and completing questionnaires.

Conditions

Advanced Solid Tumors Cancer

Keywords

Cancer; Tumor; ABBV-CLS-579; PD-1; VEGFR TKI; ccRCC; NSCLC; MSI-H; HNSCC

Outcome Measures

Primary Outcomes (24)

• Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579

  Maximum plasma/serum concentration of ABBV-CLS-579

  Baseline Up to Approximately Day 44

• Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4

  Maximum plasma/serum concentration of Metabolite M4

  Baseline Up to Approximately Day 44

• Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor

  Maximum plasma/serum concentration of PD-1 inhibitor

  Baseline Up to Approximately Day 64

• Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI

  Maximum plasma/serum concentration of VEGFR TKI

  Baseline Up to Approximately Day 64

• Time To Cmax (Tmax) Of ABBV-CLS-579

  The amount of time taken to reach Cmax

  Baseline Up to Approximately Day 44

• Time To Cmax (Tmax) Of Metabolite M4

  The amount of time taken to reach Cmax

  Baseline Up to Approximately Day 44

• Time To Cmax (Tmax) Of PD-1 Inhibitor

  The amount of time taken to reach Cmax

  Baseline Up to Approximately Day 64

• Time To Cmax (Tmax) Of VEGFR TKI

  The amount of time taken to reach Cmax

  Baseline Up to Approximately Day 64

• Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579

  Terminal phase elimination rate constant (β or Beta)

  Baseline Up to Approximately Day 44

• Terminal Phase Elimination Rate Constant (β) Of Metabolite M4

  Terminal phase elimination rate constant (β or Beta)

  Baseline Up to Approximately Day 44

• Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor

  Terminal phase elimination rate constant (β or Beta)

  Baseline Up to Approximately Day 64

• Terminal Phase Elimination Rate Constant (β) Of VEGFR TKI

  Terminal phase elimination rate constant (β or Beta)

  Baseline Up to Approximately Day 64

• Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579

  Terminal phase elimination half-life (t1/2)

  Baseline Up to Approximately Day 44

• Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4

  Terminal phase elimination half-life (t1/2)

  Baseline Up to Approximately Day 44

• Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor

  Terminal phase elimination half-life (t1/2)

  Baseline Up to Approximately Day 64

• Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI

  Terminal phase elimination half-life (t1/2)

  Baseline Up to Approximately Day 64

• Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579

  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 44

• Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4

  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 44

• Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor

  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

• Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI

  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

• Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579

  The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study

  Baseline through Study Completion (approximately 3 years)

• Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor

  The Expansion Dose and/or MTD of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study

  Baseline through Study Completion (approximately 3 years)

• Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC

  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)

• Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC

  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)

Secondary Outcomes (5)

• Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

  Baseline through Study Completion (approximately 3 years)

• Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

  Baseline through Study Completion (approximately 3 years)

• Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1

  Baseline through Study Completion (approximately 3 years)

• Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1

  Baseline through Study Completion (approximately 3 years)

• Change from Baseline QTc

  Baseline through Study Completion (approximately 3 years)

Study Arms (6)

Monotherapy Dose Escalation

EXPERIMENTAL

ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors

Drug: ABBV-CLS-579

Combination Dose Escalation with PD-1

EXPERIMENTAL

ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Drug: ABBV-CLS-579; Drug: PD-1 inhibitor

Backfill Cohorts with Monotherapy

EXPERIMENTAL

ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors

Drug: ABBV-CLS-579

Backfill Cohorts in Combination with PD-1

EXPERIMENTAL

ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Drug: ABBV-CLS-579; Drug: PD-1 inhibitor

Combination Expansion with PD-1

EXPERIMENTAL

ABBV-CLS-579 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), microsatellite instability-high (MSI-H) tumors, and advanced clear cell renal cell carcinoma (ccRCC)

Drug: ABBV-CLS-579; Drug: PD-1 inhibitor

Combination Expansion with VEGFR TKI

EXPERIMENTAL

ABBV-CLS-579 will be administered at the determined recommended dose in combination with Vascular Endothelial Growth (VEGFR) Factor Receptor Tyrosine Kinase Inhibitor (TKI) in subjects with advanced ccRCC.

Drug: ABBV-CLS-579; Drug: VEGFR TKI

Interventions

ABBV-CLS-579 DRUG

Oral Capsule

Backfill Cohorts in Combination with PD-1; Backfill Cohorts with Monotherapy; Combination Dose Escalation with PD-1; Combination Expansion with PD-1; Combination Expansion with VEGFR TKI; Monotherapy Dose Escalation

PD-1 inhibitor DRUG

Intravenous (IV) infusion

Backfill Cohorts in Combination with PD-1; Combination Dose Escalation with PD-1; Combination Expansion with PD-1

VEGFR TKI DRUG

Oral Tablet

Combination Expansion 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).
• For Monotherapy and Combination Dose Escalation:
• Histologically or cytologically proven metastatic or locally advanced tumors (with measurable disease defined by Response Evaluation Criteria In Solid Tumors \[RECIST\] v1.1), 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 Combination Dose Expansion:
• For the following tumor types, the subject must have received at least 1 prior line containing PD-1/PD-L1 target therapy.
• Indication with outcome of Prior PD-1/PD-L1 Targeted Therapy and other disease characteristics:
• NSCLC
• Relapsed: Tumors express PD-L1 (TPS ≥ 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
• Refractory: Tumors express PD-L1 (TPS ≥ 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
• ccRCC
• Relapsed or Refractory: Advanced disease (locally advanced or metastatic)
• MSI-H tumors
• Refractory: Locally advanced or metastatic MSI-H tumors whose tumors are determined to have a MSI-H status by PCR or NGS tests, or dMMR by IHC tests.
• HNSCC
• Relapsed or Refractory: Tumors express PD-L1 (CPS ≥ 1\] as determined by the FDA approved PD-L1 Agilent IHC 22C3 pharmDx kit

You may not qualify if:

• Untreated brain or meningeal metastases (participants with history of metastases are eligible provide 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.
• 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, cardiac arrythmia or peripheral artery disease.
• 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 participation in this study or would make the participant an unsuitable candidate to receive study drug.
• History of uncontrolled, clinically significant endocrinopathy.
• Known gastrointestinal disorders making absorption of oral medications problematic. Inability to swallow capsules.
• If treated with anti-programmed cell death protein-1 (aPD-1)/antiprogrammed cell death protein-ligand 1(aPD-L1) targeting or other immunostimulatory 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 interstitial lung disease or pneumonitis.
• Major surgery ≤ 28 days prior to first dose of study drug.
• Poorly controlled hypertension
• History of hemorrhage, including hemoptysis, hematemesis, or melena

Sponsors & Collaborators

• AbbVie: lead
• Calico Life Sciences LLC: collaborator

Study Sites (17)

Highlands Oncology Group Springdale

Springdale, Arkansas, 72762, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Hopital Saint-Andre

Bordeaux, 33000, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

The Chaim Sheba Medical Center

Ramat Gan, 5262100, Israel

Location

National Cancer Center Hospital East

Kashiwa-Shi, Chiba, 277-8577, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

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: June 3, 2020
• First Posted: June 4, 2020
• Study Start: June 3, 2020
• Primary Completion: August 21, 2025
• Study Completion: August 21, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); KR (1); IL (1); JP (3); ES (4); US (5); TW (1)