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

Advanced Solid Tumor Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04777994
• Other study ID #: M20-431
• Status: Recruiting
• Phase: Phase 1
• Start date: March 9, 2021
• Est. completion date: October 5, 2026

Study information

• Verified date: January 2024
• Source: Calico Life Sciences LLC
• Contact: ABBVIE CALL CENTER
• Phone: 847.283.8955
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: October 5, 2026
• Est. primary completion date: August 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor Cancer
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
France	Centre Antoine Lacassagne - Nice	Nice
France	Hospital Foch	Suresnes	Ile-de-France
France	IUCT Oncopole	Toulouse
Israel	Hadassah Medical Center	Jerusalem
Israel	The Chaim Sheba Medical Center	Ramat Gan
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama	Kimiidera
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital	Seoul
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
United States	University of Michigan Comprehensive Cancer Center Michigan Medicine	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Yale University	New Haven	Connecticut
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Lifespan Cancer Institute at Rhode Island Hospital	Providence	Rhode Island
United States	Next Oncology	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Calico Life Sciences LLC	AbbVie

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)	Maximum plasma/serum concentration of ABBV-CLS-484	Baseline Up to Approximately Day 42
Primary	Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy)	Maximum plasma/serum concentration of PD-1 inhibitor	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFRTKI (Combination therapy) Maximum plasma/serum concentration of PD-1 inhibitor	Maximum plasma/serum concentration of PD-1 inhibitor	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 42
Primary	Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 64
Primary	Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 42
Primary	Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy)	AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose	Baseline Up to Approximately Day 42
Primary	Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)	AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy)	AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484	The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy therapy dose escalation phase of the study	Baseline Up to Approximately Day 42
Primary	Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)	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	Baseline Up to Approximately Day 64
Primary	Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy)	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	Baseline Up to Approximately Day 64
Primary	Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline Up to Approximately Day 42
Primary	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)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline Up to Approximately Day 64
Primary	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)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline Up to Approximately Day 64
Secondary	Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline through Study Completion (approximately 3 years)
Secondary	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)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline through Study Completion (approximately 3 years)
Secondary	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)	ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment	Baseline through Study Completion (approximately 3 years)