First In Human Study With ABBV-CLS-579 When Given Alone Or In Combination With Programmed Cell Death-1 Inhibitor In Participants With Locally Advanced Or Metastatic Tumors

• ClinicalTrials.gov Identifier: NCT04417465
• Recruitment Status: Active, not recruiting
• First Posted: June 4, 2020
• Last Update Posted: November 25, 2020
• 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: November 25, 2020
• Actual Study Start Date: June 3, 2020
• Estimated Primary Completion Date: April 6, 2023 (Final data collection date for primary outcome measure)

Current 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

• Original Primary Outcome Measures: Same as current

Current 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

• Original Secondary Outcome Measures: Same as current
• 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 Or In Combination With Programmed Cell Death-1 Inhibitor 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 With Anti-PD-1 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 or in combination with programmed cell death protein-1 (PD-1) inhibitors in treating solid cancers.

ABBV-CLS-579 is an investigational drug being developed for the treatment of solid tumors. The study has two arms - Monotherapy and Combination Therapy. In the monotherapy arm, participants will receive ABBV-CLS-579 alone, in increasing doses. In the combination therapy arm, escalating doses of ABBV-CLS-579 will be given in combination with a PD-1 inhibitor. 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 oral ABBV-CLS-579 capsule alone or in combination with intravenous (IV) PD-1 inhibitor. Participants will receive study drug 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: Programmed Cell Death-1 (PD-1) Inhibitor
  Intravenous (IV) infusion

Study Arms

• Experimental: ABBV-CLS-579 Monotherapy
  Participants will receive escalating doses of ABBV-CLS-579
  Intervention: Drug: ABBV-CLS-579
• Experimental: ABBV-CLS-579 And Programmed Cell Death-1 (PD-1) Inhibitor
  Participants will receive escalating doses of ABBV-CLS-579 and PD-1 inhibitor.
  Interventions:

  • Drug: ABBV-CLS-579
  • Drug: Programmed Cell Death-1 (PD-1) Inhibitor

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 3, 2020): 43
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 6, 2023
• Estimated Primary Completion Date: April 6, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must weigh at least 35 kilograms (kg).
• 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 anticancer therapy for the indication being considered.
• 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 < 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 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.
• 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, pericardial effusion, pericarditis or clinically significant 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 participation in this study or would make the participant an unsuitable candidate to receive study drug.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, Japan, United States

Administrative Information

• NCT Number: NCT04417465
• Other Study ID Numbers: M20-124; 2020-000639-28 ( EudraCT Number )
• Has Data Monitoring Committee: No

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

• Responsible Party: Calico Life Sciences LLC
• Study Sponsor: Calico Life Sciences LLC
• Collaborators: AbbVie
• Investigators: Not Provided
• PRS Account: Calico Life Sciences LLC
• Verification Date: October 2020