Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) [Time frame: Baseline Up to Approximately Day 42]
• 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]
• 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]
• Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) [Time frame: Baseline Up to Approximately Day 42]
• Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) [Time frame: Baseline Up to Approximately Day 64]
• Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy) [Time frame: Baseline Up to Approximately Day 64]
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) [Time frame: Baseline Up to Approximately Day 42]
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) [Time frame: Baseline Up to Approximately Day 64]
• Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy) [Time frame: Baseline Up to Approximately Day 64]
• 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]

Secondary outcome measures (3)

• 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)]
• 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)]
• 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)]

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:

• Participants with histologically or cytologically proven metastatic or locally advanced tumors, 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 Monotherapy Dose Expansion only:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• University of Arizona Cancer Center - Tucson /ID# 262698 — Tucson
• Yale University School of Medicine /ID# 225707 — New Haven
• Johns Hopkins Hospital /ID# 254056 — Baltimore
• Beth Israel Deaconess Medical Center /ID# 252009 — Boston
• Dana-Farber Cancer Institute /ID# 249642 — Boston
• University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010 — Ann Arbor
• NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869 — New York
• Duke Cancer Center /ID# 251975 — Durham
• … and 7 more centers

France · 4 centers

• Institut Paoli-Calmettes /ID# 260956 — Marseille
• IUCT Oncopole /ID# 252673 — Toulouse
• Centre Antoine-Lacassagne /ID# 252606 — Nice
• Hopital Foch /ID# 252607 — Suresnes

Israel · 3 centers

• Rabin Medical Center /ID# 263631 — Petah Tikva
• Hadassah Medical Center /ID# 252366 — Jerusalem
• The Chaim Sheba Medical Center /ID# 226756 — Ramat Gan

South Korea · 3 centers

• Seoul National University Hospital /ID# 254635 — Seoul
• Samsung Medical Center /ID# 260664 — Seoul
• Yonsei University Health System Severance Hospital /ID# 260665 — Seoul

Spain · 3 centers

• Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524 — L'Hospitalet de Llobregat
• Hospital Universitario 12 de Octubre /ID# 257374 — Madrid
• Hospital Universitario HM Sanchinarro /ID# 228034 — Madrid

Japan · 2 centers

• National Cancer Center Hospital /ID# 225884 — Chuo-ku
• Wakayama Medical University Hospital /ID# 252988 — Wakayama

Publications

• Baumgartner CK, Ebrahimi-Nik H, Iracheta-Vellve A, Hamel KM, Olander KE, Davis TGR, McGuire KA, Halvorsen GT, Avila OI, Patel CH, Kim SY, Kammula AV, Muscato AJ, Halliwill K, Geda P, Klinge KL, Xiong Z, Duggan R, Mu L, Yeary MD, Patti JC, Balon TM, Mathew R, Backus C, Kennedy DE, Chen A, Longenecker K, Klahn JT, Hrusch CL, Krishnan N, Hutchins CW, Dunning JP, Bulic M, Tiwari P, Colvin KJ, Chuong C PMID 37794185

Identifiers

NCT: NCT04777994 · M20-431 · 2023-507568-38-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗