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

• ClinicalTrials.gov Identifier: NCT04417465
• Recruitment Status: Recruiting
• First Posted: June 4, 2020
• Last Update Posted: July 12, 2022
• Sponsor: Calico Life Sciences LLC
• Collaborator: AbbVie
• Information provided by (Responsible Party): Calico Life Sciences LLC

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 4, 2020
• Last Update Posted Date: July 12, 2022
• Actual Study Start Date: June 3, 2020
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors Cancer

Intervention

• Drug: ABBV-CLS-579
  Oral Capsule
• Drug: PD-1 inhibitor
  Intravenous (IV) infusion
• Drug: VEGFR TKI
  Oral Tablet

Study Arms

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 8, 2022): 263
• Original Estimated Enrollment (submitted: June 3, 2020): 43
• Estimated Study Completion Date: September 30, 2023
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 847.283.8955; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Israel, Japan, Korea, Republic of, Taiwan, United States

Administrative Information

• NCT Number: NCT04417465
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Calico Life Sciences LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Calico Life Sciences LLC
• Original Study Sponsor: Same as current
• Collaborators: AbbVie
• Investigators: Not Provided
• PRS Account: Calico Life Sciences LLC
• Verification Date: July 2022