First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors

Advanced Solid Tumors Cancer Clinical Trial

Official title:

A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-579 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04417465
• Other study ID #: M20-124
• Secondary ID: 2020-000639-28
• Status: Recruiting
• Phase: Phase 1
• Start date: June 3, 2020
• Est. completion date: April 30, 2026

Study information

• Verified date: December 2023
• 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 purpose of this study is to see how safe and effective ABBV-CLS-579 is when used alone and in combination with a PD-1 target agent or with a VEGF TKI. ABBV-CLS-579 is an investigational drug being developed for the treatment of tumors. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-579 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 Combination Dose Expansion. Part 1, ABBV-CLS-579 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-579 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-579 will be administered at the determined recommended dose in combination with a PD-1 target agent or with a VEGFR TKI 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). 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 study 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 263
• Est. completion date: April 30, 2026
• Est. primary completion date: August 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must weigh at least 35 kilograms (kg).
• For Monotherapy and Combination Dose Escalation:
• 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 systemic anticancer therapy for the indication being considered.
• For Combination Dose Expansion:
• For the following tumor types, the subject must have received at least 1 prior line containing PD-1/PD-L1 target therapy. Indication with outcome of Prior PD-1/PD-L1 Targeted Therapy and other disease

characteristics:

• NSCLC
• Relapsed: Tumors express PD-L1 (TPS = 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
• Refractory: Tumors express PD-L1 (TPS = 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
• ccRCC
• Relapsed or Refractory: Advanced disease (locally advanced or metastatic)
• MSI-H tumors
• Refractory: Locally advanced or metastatic MSI-H tumors whose tumors are determined to have a MSI-H status by PCR or NGS tests, or dMMR by IHC tests.
• HNSCC
• Relapsed or Refractory: Tumors express PD-L1 (CPS = 1] as determined by the FDA approved PD-L1 Agilent IHC 22C3 pharmDx kit
• For Combination Dose Expansion:
• Locally advanced or metastatic, advanced ccRCC who have relapsed after at least 1 prior VEGFR TKI therapy
• Received at least 1 prior line containing PD 1/PD L1 targeted therapy with a best response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months)
• Received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression (in the absence of best response of CR/PR/stable disease by RECIST v1.1) with PD 1/PD L1 targeted therapy
• An Eastern Cooperative Oncology Group (ECOG) performance status = 2.
• Life expectancy of = 12 weeks.
• Laboratory values meeting protocol criteria.
• If the subject is on anticoagulant therapy, INR must be within therapeutic goal.
• 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 provide 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, pericarditis, or clinically significant pericardial effusion, cardiac arrythmia or peripheral artery disease.
• 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.
• History of uncontrolled, clinically significant endocrinopathy.
• 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.
• Poorly controlled hypertension
• History of hemorrhage, including hemoptysis, hematemesis, or melena
• History of other malignancy, with the following exceptions:
• No known active disease present for 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
• Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices.

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasm Metastasis

Intervention

Drug:
• ABBV-CLS-579
Oral Capsule
• PD-1 inhibitor
Intravenous (IV) infusion
• VEGFR TKI
Oral Tablet

Locations

Country	Name	City	State
France	Hopital Saint-Andre	Bordeaux
France	Institut Gustave Roussy	Villejuif
Israel	The Chaim Sheba Medical Center	Ramat Gan
Japan	National Cancer Center Hospital	Chuo-ku, Tokyo
Japan	National Cancer Center Hospital East	Kashiwa-Shi	Chiba
Japan	Wakayama Medical University Hospital	Wakayama-Shi	Wakayama
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Taiwan	National Taiwan University Hospital	Taipei
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Yale University	New Haven	Connecticut
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Highlands Oncology Group Springdale	Springdale	Arkansas

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,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579	Maximum plasma/serum concentration of ABBV-CLS-579	Baseline Up to Approximately Day 44
Primary	Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4	Maximum plasma/serum concentration of Metabolite M4	Baseline Up to Approximately Day 44
Primary	Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor	Maximum plasma/serum concentration of PD-1 inhibitor	Baseline Up to Approximately Day 64
Primary	Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI	Maximum plasma/serum concentration of VEGFR TKI	Baseline Up to Approximately Day 64
Primary	Time To Cmax (Tmax) Of ABBV-CLS-579	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 44
Primary	Time To Cmax (Tmax) Of Metabolite M4	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 44
Primary	Time To Cmax (Tmax) Of PD-1 Inhibitor	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 64
Primary	Time To Cmax (Tmax) Of VEGFR TKI	The amount of time taken to reach Cmax	Baseline Up to Approximately Day 64
Primary	Terminal Phase Elimination Rate Constant (ß) Of ABBV-CLS-579	Terminal phase elimination rate constant (ß or Beta)	Baseline Up to Approximately Day 44
Primary	Terminal Phase Elimination Rate Constant (ß) Of Metabolite M4	Terminal phase elimination rate constant (ß or Beta)	Baseline Up to Approximately Day 44
Primary	Terminal Phase Elimination Rate Constant (ß) Of PD-1 Inhibitor	Terminal phase elimination rate constant (ß or Beta)	Baseline Up to Approximately Day 64
Primary	Terminal Phase Elimination Rate Constant (ß) Of VEGFR TKI	Terminal phase elimination rate constant (ß or Beta)	Baseline Up to Approximately Day 64
Primary	Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 44
Primary	Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 44
Primary	Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 64
Primary	Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI	Terminal phase elimination half-life (t1/2)	Baseline Up to Approximately Day 64
Primary	Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579	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 44
Primary	Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4	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 44
Primary	Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor	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	Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI	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	Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579	The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study	Baseline through Study Completion (approximately 3 years)
Primary	Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor	The Expansion Dose and/or MTD of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study	Baseline through Study Completion (approximately 3 years)
Primary	Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC	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)
Primary	Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC	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	Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1	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	Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1	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	Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1	BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence	Baseline through Study Completion (approximately 3 years)
Secondary	Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1	BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence	Baseline through Study Completion (approximately 3 years)
Secondary	Change from Baseline QTc	QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline	Baseline through Study Completion (approximately 3 years)