248 Participants Needed

ABBV-CLS-484 + PD-1/VEGFR Inhibitors for Cancer

Recruiting at 54 trial locations
AC
Overseen ByABBVIE CALL CENTER
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the drug ABBV-CLS-484 + PD-1/VEGFR inhibitors for cancer?

Research shows that combining drugs that block PD-1 (a protein that helps cancer cells hide from the immune system) with those that inhibit VEGFR (a protein that helps tumors grow blood vessels) can be effective in treating various cancers. For example, studies have found that similar combinations increase the presence of immune cells that attack cancer in lung and liver cancers.12345

Is the combination of ABBV-CLS-484 and PD-1/VEGFR inhibitors safe for humans?

PD-1 inhibitors, which are part of this treatment, have been shown to have a manageable safety profile in cancer patients, making them suitable for outpatient use. However, there have been reports of hepatitis B reactivation in some patients using PD-1 inhibitors, which could lead to treatment delays or discontinuation.46789

What makes the drug ABBV-CLS-484 unique for cancer treatment?

ABBV-CLS-484, also known as Osunprotafib, is unique because it combines with PD-1 and VEGFR inhibitors to potentially enhance the immune system's ability to fight cancer by blocking specific pathways that tumors use to grow and evade immune detection. This combination approach is different from standard treatments that typically target only one pathway.110111213

Research Team

AI

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with advanced solid tumors who've tried at least one cancer therapy without success. They must be physically capable of daily activities, weigh over 35 kg, and have a life expectancy of at least 12 weeks. Certain conditions like uncontrolled high blood pressure or recent severe illnesses exclude participation.

Inclusion Criteria

I am able to get out of my bed or chair and move around.
Laboratory values meeting protocol criteria.
QT interval corrected for heart rate < 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
See 7 more

Exclusion Criteria

I currently have an active COVID-19 infection.
I do not have ongoing severe numbness or pain in my hands or feet.
I haven't needed systemic treatment for an autoimmune disease in the last 2 years, except for thyroid issues, skin depigmentation, or severe allergies.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose Escalation

ABBV-CLS-484 is administered alone in escalating dose levels to eligible subjects with advanced solid tumors

Up to 6 weeks

Combination Dose Escalation

ABBV-CLS-484 is administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects with advanced solid tumors

Up to 9 weeks

Dose Expansion

ABBV-CLS-484 is administered at the recommended dose as monotherapy and in combination with a PD-1 targeting agent or VEGFR TKI in subjects with specific types of advanced or metastatic tumors

Up to 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • ABBV-CLS-484
  • Programmed Cell Death-1 (PD-1) Inhibitor
  • Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Trial OverviewABBV-CLS-484's safety and effectiveness are being tested alone or with other drugs targeting PD-1 or VEGFR in patients with specific cancers including head and neck squamous cell carcinoma, non-small cell lung cancer, and renal cell carcinoma. The study has three parts: dose escalation for monotherapy and combination therapy, followed by dose expansion.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Monotherapy ExpansionExperimental Treatment1 Intervention
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)
Group II: Monotherapy Dose EscalationExperimental Treatment1 Intervention
ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors
Group III: Combination Expansion with PD-1 InhibitorExperimental Treatment3 Interventions
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.
Group IV: Combination ExpansionExperimental Treatment3 Interventions
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.
Group V: Combination Dose Escalation with VEGFR TKIExperimental Treatment3 Interventions
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
Group VI: Combination Dose Escalation with PD-1 InhibitorExperimental Treatment2 Interventions
ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Find a Clinic Near You

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials
1,079
Recruited
535,000+
Founded
2013
Headquarters
North Chicago, USA
Known For
Immunology treatments
Top Products
Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael profile image

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Calico Life Sciences LLC

Industry Sponsor

Trials
11
Recruited
960+

Findings from Research

The combination of nivolumab and ipilimumab as neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC) was found to be feasible, but the study was terminated early due to significant treatment-related adverse events (TRAEs), with 67% of patients experiencing some form of toxicity.
Despite the challenges, two patients achieved a pathologic complete response (pCR) and remained disease-free for over 24 months, suggesting that further research is needed to identify biomarkers that could predict which patients are more likely to benefit from this treatment.
Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer.Reuss, JE., Anagnostou, V., Cottrell, TR., et al.[2021]
In a clinical trial involving 105 patients with advanced non-small cell lung cancer (NSCLC), the combination of apatinib and camrelizumab demonstrated promising antitumor activity, with an objective response rate of 30.9% and a median overall survival of 15.5 months.
The treatment was well-tolerated with no unexpected adverse events, and it appeared particularly effective in patients with STK11/KEAP1 mutations, suggesting that this genetic profile may predict better outcomes with the combination therapy.
Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy.Zhou, C., Wang, Y., Zhao, J., et al.[2022]
In a study of 46 patients with advanced NSCLC and Del19-EGFR, afatinib showed a high objective response rate of 78.2% and a median progression-free survival of 20.5 months, indicating its efficacy as a first-line treatment.
Older patients (≥70 years) experienced similar benefits from afatinib as younger patients, with manageable side effects, although they required more dose reductions, suggesting afatinib is a viable treatment option for older adults with this condition.
Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician Lung Cancer Group.Agraso, S., Lázaro, M., Firvida, XL., et al.[2022]

References

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer. [2021]
Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy. [2022]
Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician Lung Cancer Group. [2022]
Immune checkpoint inhibitors combined with angiogenic inhibitors in the treatment of locally advanced or metastatic lung adenocarcinoma patients. [2023]
Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma. [2021]
Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China. [2021]
Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]
Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]
Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Effects of PD-1 inhibitor combined with anti-angiogenic drugs on efficacy and immune function of non-small cell lung cancer. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG Oncology/Gynecologic Oncology Group study. [2022]
Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study. [2022]
Clinical Study on the Efficacy of Bevacizumab in Combination with Pembrolizumab on Cellular Immune Function in the Treatment of Driver Gene-Negative Stage IV Lung Adenocarcinoma. [2022]