[M20-431] A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors

Recruiting

• Conditions: Advanced Solid Tumor

• Registration Number: jRCT2031210036
• Lead Sponsor: Calico Life Sciences LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-13
• Study Start: 2021-05-19
• Last Update Posted: 2022-10-20

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 248

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:

  • Known active disease present for >= 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.

Study & Design

• Study Type: Interventional
• Study Design: single assignment

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484		Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor		Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy)
Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI		Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI (Combination therapy)
Time To Cmax (Tmax) Of ABBV-CLS-484		Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
Time To Cmax (Tmax) Of PD-1 Inhibitor		Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
Time to Cmax (Tmax) of VEGFR TKI		Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)
Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484		Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor		Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI		Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484		Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy)
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor		Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)
Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI		Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy)
Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484		Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484
Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor		Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)
Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI		Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy)
Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1		Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1		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)
Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1		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)

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)		Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
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)		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)
Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)		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)