Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors
- Conditions
- Advanced Solid Tumor Cancer
- Interventions
- Drug: Programmed Cell Death-1 (PD-1) InhibitorDrug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
- Registration Number
- NCT04777994
- Lead Sponsor
- Calico Life Sciences LLC
- Brief Summary
The study will assess the safety, PK, PD, and preliminary efficacy of ABBVCLS-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 ABBVCLS-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 available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 248
- 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
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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.
-
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)
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Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
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Unresolved Grade 2 or higher peripheral neuropathy.
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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.
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Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
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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.
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History of uncontrolled, clinically significant endocrinopathy.
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Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy Dose Escalation ABBV-CLS-484 ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors Combination Dose Escalation with PD-1 Inhibitor Programmed Cell Death-1 (PD-1) Inhibitor ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors Combination Expansion Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) 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. Combination Dose Escalation with VEGFR TKI Programmed Cell Death-1 (PD-1) Inhibitor 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 Combination Expansion with PD-1 Inhibitor Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) 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. Combination Dose Escalation with PD-1 Inhibitor ABBV-CLS-484 ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors Combination Expansion ABBV-CLS-484 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. Monotherapy Expansion ABBV-CLS-484 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) Combination Expansion with PD-1 Inhibitor ABBV-CLS-484 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. Combination Dose Escalation with VEGFR TKI ABBV-CLS-484 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
- Primary Outcome Measures
Name Time Method Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) 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) Baseline Up to Approximately Day 64 Maximum plasma/serum concentration of PD-1 inhibitor
Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) 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) Baseline Up to Approximately Day 64 The amount of time taken to reach Cmax
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy) Baseline Up to Approximately Day 64 Terminal phase elimination half-life (t1/2)
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFRTKI (Combination therapy) Maximum plasma/serum concentration of PD-1 inhibitor 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) Baseline Up to Approximately Day 42 The amount of time taken to reach Cmax
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) 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 PD-1 Inhibitor (Combination therapy) 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) 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 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 Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy) 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 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) 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: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) Baseline Up to Approximately Day 42 Terminal phase elimination half-life (t1/2)
Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy) 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 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) 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: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy) 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) 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
- Secondary Outcome Measures
Name Time Method 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) 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 Based On (RECIST) v1.1 (Monotherapy) 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) 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
Trial Locations
- Locations (30)
The Chaim Sheba Medical Center /ID# 226756
🇮🇱Ramat Gan, Tel-Aviv, Israel
University of Arizona Cancer Center - Tucson /ID# 262698
🇺🇸Tucson, Arizona, United States
Yale University School of Medicine /ID# 225707
🇺🇸New Haven, Connecticut, United States
Johns Hopkins Hospital /ID# 254056
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center /ID# 252009
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute /ID# 249642
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
🇺🇸Ann Arbor, Michigan, United States
NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
🇺🇸New York, New York, United States
Duke Cancer Center /ID# 251975
🇺🇸Durham, North Carolina, United States
Carolina BioOncology Institute /ID# 225704
🇺🇸Huntersville, North Carolina, United States
Perelman Center for Advanced Medicine /ID# 250188
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Ctr /ID# 225706
🇺🇸Pittsburgh, Pennsylvania, United States
Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705
🇺🇸Providence, Rhode Island, United States
University of Texas Southwestern Medical Center /ID# 251974
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center /ID# 252004
🇺🇸Houston, Texas, United States
NEXT Oncology /ID# 225708
🇺🇸San Antonio, Texas, United States
Institut Paoli-Calmettes /ID# 260956
🇫🇷Marseille, Bouches-du-Rhone, France
IUCT Oncopole /ID# 252673
🇫🇷Toulouse Cedex 9, Occitanie, France
Centre Antoine-Lacassagne /ID# 252606
🇫🇷Nice, Provence-Alpes-Cote-d Azur, France
Hopital Foch /ID# 252607
🇫🇷Suresnes CEDEX, France
Rabin Medical Center /ID# 263631
🇮🇱Petah Tikva, HaMerkaz, Israel
Hadassah Medical Center /ID# 252366
🇮🇱Jerusalem, Yerushalayim, Israel
National Cancer Center Hospital /ID# 225884
🇯🇵Chuo-ku, Tokyo, Japan
Wakayama Medical University Hospital /ID# 252988
🇯🇵Wakayama-shi, Wakayama, Japan
Seoul National University Hospital /ID# 254635
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 260664
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 260665
🇰🇷Seoul, Korea, Republic of
Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario 12 de Octubre /ID# 257374
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro /ID# 228034
🇪🇸Madrid, Spain