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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04417465
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : July 12, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Calico Life Sciences LLC

Tracking Information
First Submitted Date  ICMJE June 3, 2020
First Posted Date  ICMJE June 4, 2020
Last Update Posted Date July 12, 2022
Actual Study Start Date  ICMJE June 3, 2020
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2022)
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Maximum plasma/serum concentration of ABBV-CLS-579
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Maximum plasma/serum concentration of Metabolite M4
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Maximum plasma/serum concentration of PD-1 inhibitor
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI [ Time Frame: Baseline Up to Approximately Day 64 ]
    Maximum plasma/serum concentration of VEGFR TKI
  • Time To Cmax (Tmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    The amount of time taken to reach Cmax
  • Time To Cmax (Tmax) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]
    The amount of time taken to reach Cmax
  • Time To Cmax (Tmax) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    The amount of time taken to reach Cmax
  • Time To Cmax (Tmax) Of VEGFR TKI [ Time Frame: Baseline Up to Approximately Day 64 ]
    The amount of time taken to reach Cmax
  • Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Rate Constant (β) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Rate Constant (β) Of VEGFR TKI [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination half-life (t1/2)
  • Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination half-life (t1/2)
  • Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination half-life (t1/2)
  • Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination half-life (t1/2)
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4 [ Time Frame: Baseline Up to Approximately Day 44 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI [ Time Frame: Baseline Up to Approximately Day 64 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study
  • Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    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
  • 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 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
  • Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Original Primary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Maximum plasma/serum concentration of ABBV-CLS-579
  • Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Maximum plasma/serum concentration of PD-1 inhibitor
  • Time To Cmax (Tmax) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    The amount of time taken to reach Cmax
  • Time To Cmax (Tmax) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    The amount of time taken to reach Cmax
  • Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination rate constant (β or Beta)
  • Terminal Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    Terminal phase elimination half-life (t1/2)
  • Terminal Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    Terminal phase elimination half-life (t1/2)
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579 [ Time Frame: Baseline Up to Approximately Day 44 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor [ Time Frame: Baseline Up to Approximately Day 64 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
  • Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-579 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    The MTD and/or RP2D of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study
  • Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    The MTD and/or RP2D of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2022)
  • Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
  • Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
  • Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
  • Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
  • Change from Baseline QTc [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
  • Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
  • Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
  • Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
  • Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1 [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
  • Change from Baseline QTc [ Time Frame: Baseline Up to Approximately Day 44 ]
    QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors
Official Title  ICMJE A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-579 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors Cancer
Intervention  ICMJE
  • Drug: ABBV-CLS-579
    Oral Capsule
  • Drug: PD-1 inhibitor
    Intravenous (IV) infusion
  • Drug: VEGFR TKI
    Oral Tablet
Study Arms  ICMJE
  • Experimental: Monotherapy Dose Escalation
    ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors
    Intervention: Drug: ABBV-CLS-579
  • Experimental: Combination Dose Escalation with PD-1
    ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
    Interventions:
    • Drug: ABBV-CLS-579
    • Drug: PD-1 inhibitor
  • Experimental: Backfill Cohorts with Monotherapy
    ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors
    Intervention: Drug: ABBV-CLS-579
  • Experimental: Backfill Cohorts in Combination with PD-1
    ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
    Interventions:
    • Drug: ABBV-CLS-579
    • Drug: PD-1 inhibitor
  • Experimental: Combination Expansion with PD-1
    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)
    Interventions:
    • Drug: ABBV-CLS-579
    • Drug: PD-1 inhibitor
  • Experimental: Combination Expansion with VEGFR TKI
    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.
    Interventions:
    • Drug: ABBV-CLS-579
    • Drug: VEGFR TKI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2022)
263
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2020)
43
Estimated Study Completion Date  ICMJE September 30, 2023
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • For Combination Dose Expansion:

    • Locally advanced or metastatic, advanced ccRCC who have relapsed after at least 1 prior VEGFR TKI therapy
  • Received at least 1 prior line containing PD 1/PD L1 targeted therapy with a best response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months)
  • Received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression (in the absence of best response of CR/PR/stable disease by RECIST v1.1) with PD 1/PD L1 targeted therapy
  • An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Life expectancy of ≥ 12 weeks.
  • Laboratory values meeting protocol criteria.
  • If the subject is on anticoagulant therapy, INR must be within therapeutic goal.
  • QT interval corrected for heart rate < 450 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.

Exclusion Criteria:

  • 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
  • History of other malignancy, with the following exceptions:

    • No known active disease present for 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
  • Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Israel,   Japan,   Korea, Republic of,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04417465
Other Study ID Numbers  ICMJE M20-124
2020-000639-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Calico Life Sciences LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Calico Life Sciences LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE AbbVie
Investigators  ICMJE Not Provided
PRS Account Calico Life Sciences LLC
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP