A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors

• ClinicalTrials.gov Identifier: NCT04777994
• Recruitment Status: Recruiting
• First Posted: March 2, 2021
• Last Update Posted: January 31, 2024
• Sponsor: Calico Life Sciences LLC
• Collaborator: AbbVie
• Information provided by (Responsible Party): Calico Life Sciences LLC

Tracking Information

• First Submitted Date: February 25, 2021
• First Posted Date: March 2, 2021
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: March 9, 2021
• Estimated Primary Completion Date: August 18, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 12, 2022)

• Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  Maximum plasma/serum concentration of ABBV-CLS-484
• 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 ]
  Maximum plasma/serum concentration of PD-1 inhibitor
• 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 ]
  Maximum plasma/serum concentration of PD-1 inhibitor
• Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  The amount of time taken to reach Cmax
• Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  The amount of time taken to reach Cmax
• Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  The amount of time taken to reach Cmax
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  Terminal phase elimination half-life (t1/2)
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  Terminal phase elimination half-life (t1/2)
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  Terminal phase elimination half-life (t1/2)
• 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 ]
  AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
• 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 ]
  AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
• 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 ]
  AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
• Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 [ Time Frame: Baseline Up to Approximately Day 42 ]
  The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy therapy dose escalation phase of the study
• 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 ]
  The MTD and/or RP2D of ABBV-CLS-484 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
• 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 ]
  The MTD and/or RP2D of ABBV-CLS-484 and VEGFR TKI will be determined during the combination therapy dose escalation phase of the study
• 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 ]
  ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
• 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 ]
  ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
• 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 ]
  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: February 26, 2021)

• Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  Maximum plasma/serum concentration of ABBV-CLS-484
• 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 ]
  Maximum plasma/serum concentration of PD-1 inhibitor
• Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  The amount of time taken to reach Cmax
• Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  The amount of time taken to reach Cmax
• Dose Escalation: Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  Terminal phase elimination rate constant (β or Beta)
• Dose Escalation: Phase Elimination Rate Constant (β) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  Terminal phase elimination rate constant (β or Beta)
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  Terminal phase elimination half-life (t1/2)
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
  Terminal phase elimination half-life (t1/2)
• Dose Escalation: Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
• 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 ]
  AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
• Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
  The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy dose escalation phase of the study
• 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 ]
  The MTD and/or RP2D of ABBV-CLS-484 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
• 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 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
• 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 ]
  ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment

Current Secondary Outcome Measures (submitted: May 12, 2022)

• Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy) [ 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
• Dose Escalation: 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 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
• 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 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 Secondary Outcome Measures (submitted: February 26, 2021)

• Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy) [ 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
• Dose Escalation: 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 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
• Official Title: A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

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.

• 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 Tumor Cancer

Intervention

• Drug: ABBV-CLS-484
  Oral Capsule
• Drug: Programmed Cell Death-1 (PD-1) Inhibitor
  Intravenous (IV) infusion
• Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
  Oral Tablet

Study Arms

• Experimental: Monotherapy Dose Escalation
  ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors
  Intervention: Drug: ABBV-CLS-484
• 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
  Interventions:

  • Drug: ABBV-CLS-484
  • Drug: Programmed Cell Death-1 (PD-1) Inhibitor
• 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)
  Intervention: Drug: ABBV-CLS-484
• 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.
  Interventions:

  • Drug: ABBV-CLS-484
  • Drug: Programmed Cell Death-1 (PD-1) Inhibitor
• 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
  Interventions:

  • Drug: ABBV-CLS-484
  • Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
• 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:

  • Drug: ABBV-CLS-484
  • Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 12, 2022): 248
• Original Estimated Enrollment (submitted: February 26, 2021): 100
• Estimated Study Completion Date: October 5, 2026
• Estimated Primary Completion Date: August 18, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

• Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.

For Monotherapy Dose Expansion only:

• Subjects 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
• Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
• Subjects 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.

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: France, Israel, Japan, Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT04777994
• Other Study ID Numbers: M20-431
• 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

• IPD Sharing Statement: Not Provided
• 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: January 2024