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

Recruiting in Palo Alto (17 mi)

+54 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AbbVie

Must not be taking: Steroids, Immune-oncology agents

Disqualifiers: Brain metastases, Hepatitis, HIV, others

No Placebo Group

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. ^{1 2 3 4 5}

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. ^{4 6 7 8 9}

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. ^{1 10 11 12 13}

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.

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.

Trial 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 (Monoclonal Antibodies)
• Programmed Cell Death-1 (PD-1) Inhibitor (Monoclonal Antibodies)
• Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) (Tyrosine Kinase Inhibitor)

Trial Overview ABBV-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

Group I: Monotherapy Expansion Experimental Treatment 1 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 Escalation Experimental Treatment 1 Intervention

ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors

Group III: Combination Expansion with PD-1 Inhibitor Experimental Treatment 3 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 Expansion Experimental Treatment 3 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 TKI Experimental Treatment 3 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 Inhibitor Experimental Treatment 2 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

Research Locations Nearby Select from list below to view details:

University of Arizona Cancer Center - Tucson /ID# 262698 Tucson, AZ

Yale University School of Medicine /ID# 225707 New Haven, CT

Johns Hopkins Hospital /ID# 254056 Baltimore, MD

Beth Israel Deaconess Medical Center /ID# 252009 Boston, MA

More Trial Locations

Who Is Running the Clinical Trial?

AbbVie Lead Sponsor

Calico Life Sciences LLC Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer. [2021] We conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab.

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy. [2022] Label="PURPOSE">Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8+ T cells and reducing recruitment of tumor-associated macrophages. We hereby conducted a clinical trial to evaluate this combination in pretreated patients with advanced non-small cell lung cancer (NSCLC).

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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] In clinical studies, first-line afatinib demonstrated efficacy in Del19-EGFR NSCLC.

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5. England pubmed.ncbi.nlm.nih.gov

Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma. [2021] Combining inhibitors of vascular endothelial growth factor and the programmed cell death protein 1 (PD1) pathway has shown efficacy in multiple cancers, but the disease-specific and agent-specific mechanisms of benefit remain unclear. We examined the efficacy and defined the mechanisms of benefit when combining regorafenib (a multikinase antivascular endothelial growth factor receptor inhibitor) with PD1 blockade in murine hepatocellular carcinoma (HCC) models.

6. Germany pubmed.ncbi.nlm.nih.gov

Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China. [2021] This study evaluated the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockade for the treatment of small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).

7. Greece pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023] To explore the safety of osimertinib plus ramucirumab in patients with EGFR-mutated lung adenocarcinoma.

8. United States pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023] There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P

9. United States pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022] The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in the tumor microenvironment. Drugs designed to block PD-1 or PD-L1 "release the brakes" on anti-tumor immunity and have demonstrated clinical activity in several types of advanced cancers, validating this pathway as a target for cancer therapy. Two such drugs have recently been approved to treat melanoma and lung cancers, and regulatory approvals in first- and second-line settings for additional cancer types are anticipated. The manageable safety profile of PD-1/PD-L1 blocking drugs identifies them as suitable for outpatient administration and the development of combinatorial therapies. Ongoing studies aim to identify biomarkers to guide patient selection, which would further improve the risk:benefit ratio for these drugs.

10. United States pubmed.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] To investigate the effect of PD-1 inhibitor combined with anti-angiogenic drugs on the therapeutic efficacy and immune function of patients with non-small cell lung cancer (NSCLC).

11. United States pubmed.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] Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients.

12. England pubmed.ncbi.nlm.nih.gov

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] The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).

13. Egypt pubmed.ncbi.nlm.nih.gov

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] To explore the efficacy of bevacizumab in combination with PD-1 immune drug pembrolizumab on cellular immune function in the treatment of driver gene-negative stage IV lung adenocarcinoma and its short-term survival effect.