Advanced Solid Tumor CancerPhase 1NCT04777994
Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors
A Phase 1 study testing ABBV-CLS-484, Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) and Programmed Cell Death-1 (PD-1) Inhibitor in people with Advanced Solid Tumor Cancer, run by Calico Life Sciences LLC at 30 sites in 6 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor Cancer
- What is being tested?
- ABBV-CLS-484, Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) and Programmed Cell Death-1 (PD-1) Inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 30 sitesin 6 countries
- Study dates
- 9 Mar 2021to Oct 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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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.
- 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.
Trial locations and contacts
30 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 6 countries
United States15 sites, 13 recruiting
- Recruiting
University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
Ann Arbor, Michigan, 48109
- Recruiting
Johns Hopkins Hospital /ID# 254056
Baltimore, Maryland, 21287
Site Coordinator, 443-287-8312
- Recruiting
Beth Israel Deaconess Medical Center /ID# 252009
Boston, Massachusetts, 02215-5400
- Recruiting
Dana-Farber Cancer Institute /ID# 249642
Boston, Massachusetts, 02215
- Recruiting
University of Texas Southwestern Medical Center /ID# 251974
Dallas, Texas, 75390-7208
- Recruiting
Duke Cancer Center /ID# 251975
Durham, North Carolina, 27710
Site Coordinator, (919) 681-7460
- Recruiting
University of Texas MD Anderson Cancer Center /ID# 252004
Houston, Texas, 77030
Site Coordinator, 713-792-2121
- Completed
Carolina BioOncology Institute /ID# 225704
Huntersville, North Carolina, 28078
- Recruiting
Yale University School of Medicine /ID# 225707
New Haven, Connecticut, 06510
- Recruiting
NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
New York, New York, 10016
Site Coordinator, (212)-731-6230
- Recruiting
Perelman Center for Advanced Medicine /ID# 250188
Philadelphia, Pennsylvania, 19104
Site Coordinator, (215) 316-5151
- Recruiting
UPMC Hillman Cancer Ctr /ID# 225706
Pittsburgh, Pennsylvania, 15232
- Recruiting
Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705
Providence, Rhode Island, 02903-4923
- Completed
NEXT Oncology /ID# 225708
San Antonio, Texas, 78229
- Recruiting
University of Arizona Cancer Center - Tucson /ID# 262698
Tucson, Arizona, 85724
France4 sites, 4 recruiting
- Recruiting
Institut Paoli-Calmettes /ID# 260956
Marseille, Bouches-du-Rhone, 13009
- Recruiting
Centre Antoine-Lacassagne /ID# 252606
Nice, Provence-Alpes-Côte d'Azur Region, 06189
- Recruiting
Hopital Foch /ID# 252607
Suresnes, 92151
- Recruiting
IUCT Oncopole /ID# 252673
Toulouse, Occitanie, 31059
Israel3 sites, 3 recruiting
- Recruiting
Hadassah Medical Center /ID# 252366
Jerusalem, Jerusalem, 91120
- Recruiting
Rabin Medical Center /ID# 263631
Petah Tikva, Central District, 4941492
- Recruiting
The Chaim Sheba Medical Center /ID# 226756
Ramat Gan, Tel Aviv, 5265601
South Korea3 sites, 3 recruiting
- Recruiting
Seoul National University Hospital /ID# 254635
Seoul, Seoul Teugbyeolsi, 03080
- Recruiting
Samsung Medical Center /ID# 260664
Seoul, Seoul Teugbyeolsi, 06351
- Recruiting
Yonsei University Health System Severance Hospital /ID# 260665
Seoul, 03722
Spain3 sites, 3 recruiting
- Recruiting
Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524
L'Hospitalet de Llobregat, Barcelona, 08907
- Recruiting
Hospital Universitario 12 de Octubre /ID# 257374
Madrid, Madrid, 28041
- Recruiting
Hospital Universitario HM Sanchinarro /ID# 228034
Madrid, Madrid, 28050
Japan2 sites, 2 recruiting
- Recruiting
National Cancer Center Hospital /ID# 225884
Chuo-ku, Tokyo, 104-0045
- Recruiting
Wakayama Medical University Hospital /ID# 252988
Wakayama, Wakayama, 641-8510
About this study
Official title: A Phase 1 Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors
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).
Read more
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.
- Conditions
- Advanced Solid Tumor Cancer
- Being tested
- ABBV-CLS-484, Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI), Programmed Cell Death-1 (PD-1) Inhibitor
- Keywords
- Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
- Medical subject headings
- Neoplasms, Carcinoma, Renal Cell, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABBV-CLS-484Drug
Oral Capsule
Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)Drug
Oral Tablet
Programmed Cell Death-1 (PD-1) InhibitorDrug
Intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy Dose Escalation | Experimental | ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors Receives: Drug: ABBV-CLS-484 |
| Combination Dose Escalation with PD-1 Inhibitor | Experimental | ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors Receives: Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor |
| Monotherapy Expansion | Experimental | 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) Receives: Drug: ABBV-CLS-484 |
| Combination Expansion with PD-1 Inhibitor | Experimental | 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. Receives: Drug: ABBV-CLS-484; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) |
| Combination Dose Escalation with VEGFR TKI | Experimental | 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 Receives: Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor |
| Combination Expansion | Experimental | 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. Receives: Drug: ABBV-CLS-484; Drug: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
Maximum plasma/serum concentration of ABBV-CLS-484
Measured: Baseline Up to Approximately Day 42
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
Measured: 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
Maximum plasma/serum concentration of PD-1 inhibitor
Measured: Baseline Up to Approximately Day 64
Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
The amount of time taken to reach Cmax
Measured: Baseline Up to Approximately Day 42
Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
The amount of time taken to reach Cmax
Measured: Baseline Up to Approximately Day 64
Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)
The amount of time taken to reach Cmax
Measured: Baseline Up to Approximately Day 64
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
Terminal phase elimination half-life (t1/2)
Measured: Baseline Up to Approximately Day 42
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
Terminal phase elimination half-life (t1/2)
Measured: Baseline Up to Approximately Day 64
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
Terminal phase elimination half-life (t1/2)
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 42
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
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 42
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
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 42
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
Measured: Baseline Up to Approximately Day 64
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
Measured: Baseline Up to Approximately Day 64
Secondary outcomes (3)
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
Measured: 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)
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Measured: 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)
ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Measured: Baseline through Study Completion (approximately 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2021
- Study start9 Mar 2021
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumor CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 248 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Calico Life Sciences LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Calico Life Sciences LLC, Study director, Calico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04777994
- Sponsor's protocol ID
- M20-431
- Other IDs
- 2023-507568-38-00, 2023
- Status last verified
- Dec 2025
- First submitted
- 25 Feb 2021
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 CL, Kohnle IC, Rees MG, Boghossian A, Ronan M, Roth JA, Wu MJ, Suermondt JSMT, Knudsen NH, Cheruiyot CK, Sen DR, Griffin GK, Golub TR, El-Bardeesy N, Decker JH, Yang Y, Guffroy M, Fossey S, Trusk P, Sun IM, Liu Y, Qiu W, Sun Q, Paddock MN, Farney EP, Matulenko MA, Beauregard C, Frost JM, Yates KB, Kym PR, Manguso RT. The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature. 2023 Oct;622(7984):850-862. doi: 10.1038/s41586-023-06575-7. Epub 2023 Oct 4.
PubMed 37794185
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors
- ClinicalTrials.gov ID
- NCT04777994
- Acronym / sponsor ID
- M20-431
- Conditions
- Advanced Solid Tumor Cancer
- Keywords
- Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 248 participants (estimated)
- Lead sponsor
- Calico Life Sciences LLCIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 2 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Monotherapy Dose Escalation | Experimental | Drug: ABBV-CLS-484ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors |
| Combination Dose Escalation with PD-1 Inhibitor | Experimental | Drug: ABBV-CLS-484, Drug: Programmed Cell Death-1 (PD-1) InhibitorABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors |
| Monotherapy Expansion | Experimental | Drug: ABBV-CLS-484ABBV-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 | Experimental | Drug: ABBV-CLS-484, Drug: 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 VEGFR TKI | Experimental | Drug: ABBV-CLS-484, Drug: Programmed Cell Death-1 (PD-1) InhibitorABBV-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 | Experimental | Drug: ABBV-CLS-484, Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABBV-CLS-484Oral Capsule | Drug | Combination Dose Escalation with PD-1 Inhibitor, Combination Dose Escalation with VEGFR TKI, Combination Expansion, Combination Expansion with PD-1 Inhibitor, Monotherapy Dose Escalation, Monotherapy Expansion |
| Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)Oral Tablet | Drug | Combination Expansion, Combination Expansion with PD-1 Inhibitor |
| Programmed Cell Death-1 (PD-1) InhibitorIntravenous (IV) infusion | Drug | Combination Dose Escalation with PD-1 Inhibitor, Combination Dose Escalation with VEGFR TKI |
Primary outcome
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
Time frame: 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)
Time frame: Baseline Up to Approximately Day 64
Maximum plasma/serum concentration of PD-1 inhibitor
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
Maximum plasma/serum concentration of PD-1 inhibitor
Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
Time frame: Baseline Up to Approximately Day 42
The amount of time taken to reach Cmax
Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
Time frame: 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)
Time frame: Baseline Up to Approximately Day 64
The amount of time taken to reach Cmax
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
Time frame: Baseline Up to Approximately Day 42
Terminal phase elimination half-life (t1/2)
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
Time frame: Baseline Up to Approximately Day 64
Terminal phase elimination half-life (t1/2)
Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
Time frame: 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 ABBV-CLS-484 (Monotherapy)
Time frame: 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 Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)
Time frame: 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)
Time frame: 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
Time frame: 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 Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)
Time frame: 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)
Time frame: 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
Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
Time frame: 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 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)
Time frame: 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: 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 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
3 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Derived from this study: PubMed 37794185Baumgartner 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 CL, Kohnle IC, Rees MG, Boghossian A, Ronan M, Roth JA, Wu MJ, Suermondt JSMT, Knudsen NH, Cheruiyot CK, Sen DR, Griffin GK, Golub TR, El-Bardeesy N, Decker JH, Yang Y, Guffroy M, Fossey S, Trusk P, Sun IM, Liu Y, Qiu W, Sun Q, Paddock MN, Farney EP, Matulenko MA, Beauregard C, Frost JM, Yates KB, Kym PR, Manguso RT. The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature. 2023 Oct;622(7984):850-862. doi: 10.1038/s41586-023-06575-7. Epub 2023 Oct 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Calico Life Sciences LLC study director
Calico
30 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABBV-CLS-484, Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) and Programmed Cell Death-1 (PD-1) Inhibitor in people with Advanced Solid Tumor Cancer, run by Calico Life Sciences LLC at 30 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, France, Israel, South Korea, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicole Director Clinical Operations (650-754-6200, info@calicolabs.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) (time frame: Baseline Up to Approximately Day 42). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04777994, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.