ABBV-CLS-579 for Cancer

Recruiting at 18 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: PD-1/PD-L1 therapy

Must not be taking: Steroids, Immunostimulatory agents

Disqualifiers: Brain metastases, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

101 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and effectiveness of ABBV-CLS-579, a new drug for treating tumors. It includes patients with advanced cancers that haven't responded to other treatments. The drug is tested alone and with other cancer therapies to see if it can help the immune system fight cancer or cut off the tumor's blood supply.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy, your INR (a blood test that measures how long it takes blood to clot) must be within the therapeutic goal. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug ABBV-CLS-579 for cancer?

Research shows that drugs similar to ABBV-CLS-579, like pembrolizumab and nivolumab, which are PD-1 inhibitors (drugs that help the immune system attack cancer cells), have improved survival rates in various cancers, such as cervical and lung cancer. This suggests that ABBV-CLS-579 might also be effective in treating cancer. ^{1 2 3 4 5}

What safety data exists for ABBV-CLS-579 or similar treatments like PD-1 inhibitors?

There is no specific safety data available for ABBV-CLS-579 or similar treatments like PD-1 inhibitors in the provided research articles. ^{6 7 8 9 10}

Eligibility Criteria

Adults with certain advanced solid tumors, including specific types of lung cancer (NSCLC), head and neck cancer (HNSCC), and kidney cancer (ccRCC) that have not responded to standard treatments or for which no effective treatment exists. Participants must have tried a PD-1/PD-L1 therapy before, weigh at least 35 kg, have an ECOG performance status ≤2, life expectancy ≥12 weeks, meet laboratory value criteria, and be able to swallow capsules.

Inclusion Criteria

Laboratory values meeting protocol criteria

I have had at least one treatment targeting PD-1/PD-L1 for my cancer type.

My advanced cancer has no standard treatment left, but I've had at least one cancer treatment before.

Exclusion Criteria

I have had cancer before, but it fits the exceptions.

I have a digestive issue that affects my ability to absorb pills or swallow capsules.

I have had bleeding issues, like coughing up blood or bloody stools.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose Escalation

ABBV-CLS-579 is administered alone in escalating dose levels to eligible subjects with advanced solid tumors

Up to 44 days

Regular visits for assessments and monitoring

Combination Dose Escalation

ABBV-CLS-579 is administered in combination with a PD-1 targeting agent in escalating dose levels to eligible subjects with advanced solid tumors

Up to 64 days

Regular visits for assessments and monitoring

Combination Dose Expansion

ABBV-CLS-579 is administered at the recommended dose in combination with a PD-1 target agent or with a VEGFR TKI in subjects with specific advanced cancers

Up to 64 days

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ABBV-CLS-579
• PD-1 inhibitor
• VEGFR TKI

Trial Overview The trial is testing ABBV-CLS-579 alone and in combination with a PD-1 inhibitor or VEGFR TKI on patients with advanced tumors. It's divided into three parts: dose escalation of ABBV-CLS-579 alone; dose escalation in combination with a PD-1 inhibitor; and expansion using the best dose found along with either a PD-1 inhibitor or VEGFR TKI for specific cancers.

Participant Groups

Group I: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors

Group II: Combination Expansion with VEGFR TKI Experimental Treatment 2 Interventions

ABBV-CLS-579 will be administered at the determined recommended dose in combination with Vascular Endothelial Growth (VEGFR) Factor Receptor Tyrosine Kinase Inhibitor (TKI) in subjects with advanced ccRCC.

Group III: Combination Expansion with PD-1 Experimental Treatment 2 Interventions

ABBV-CLS-579 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), microsatellite instability-high (MSI-H) tumors, and advanced clear cell renal cell carcinoma (ccRCC)

Group IV: Combination Dose Escalation with PD-1 Experimental Treatment 2 Interventions

ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Group V: Backfill Cohorts with Monotherapy Experimental Treatment 1 Intervention

ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors

Group VI: Backfill Cohorts in Combination with PD-1 Experimental Treatment 2 Interventions

ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

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

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 immune checkpoint inhibitor COM701, which targets the PVRIG protein, has demonstrated early signs of effectiveness in treating advanced solid tumors in an ongoing phase I trial.

COM701 shows potential for enhanced efficacy when used in combination with nivolumab, suggesting a promising approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COM701 Shows Antitumor Activity, +/- Nivolumab. [2021]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

A large-scale retrospective study of 2094 cases from the FDA adverse event reporting system found that combining immune checkpoint inhibitors with bevacizumab significantly increases the risk of adverse drug reactions (ADRs) in cancer patients, particularly interstitial lung disease, hypertension, and gastrointestinal bleeding.

The study highlights that combination therapy is an independent risk factor for these ADRs, suggesting the need for careful monitoring and individualized management strategies for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. Gu, T., Jiang, A., Zhou, C., et al.[2023]

A large-scale analysis of 16,196 serious adverse drug reaction reports identified 36 potential safety signals associated with ibrutinib, including ischemic heart diseases and fractures, highlighting the need for careful patient monitoring.

The study found that over half of the reports resulted in hospitalization, indicating that while ibrutinib is a standard treatment for B-cell malignancies, its safety profile requires further investigation to confirm these findings in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Allouchery, M., Tomowiak, C., Lombard, T., et al.[2021]

Bamlanivimab (BAM) has a higher number of adverse event signals compared to bamlanivimab/etesevimab (BAM/ETE), with specific risks like atrial fibrillation and tachycardia associated with BAM but not BAM/ETE.

While BAM/ETE is generally considered safe, potential safety signals such as acute respiratory failure and infusion-related reactions have been identified and warrant long-term monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database. Zhao, Y., Wang, H., Zhang, Q., et al.[2023]

In a study of 158 previously untreated CLL patients, the combination of obinutuzumab and bendamustine (G-B) showed an overall response rate of 81.0% and a 2-year progression-free survival rate of 81.8%, indicating strong clinical efficacy.

While G-B treatment had manageable toxicity, with 82.3% of patients experiencing grade ≥3 adverse events, careful monitoring for tumor lysis syndrome (TLS) was necessary due to its occurrence in 8.2% of patients, including two fatalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the GREEN study. Stilgenbauer, S., Leblond, V., Foà, R., et al.[2023]

A comparison of 551 patients from a healthcare claims database and 951 patients from a conventional post-marketing surveillance study showed that while patient characteristics and drug use were similar, there were significant differences in the reported adverse events (AEs) for eribulin mesylate, particularly for nausea and neutropenia.

The study suggests that healthcare claims databases can effectively complement traditional post-marketing surveillance in monitoring the safety profile of eribulin, but highlights the need for better definitions of AEs like neutropenia based on laboratory data to improve accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a Healthcare Claims Database for Post-Marketing Safety Assessments of Eribulin in Japan: A Comparative Assessment with a Prospective Post-Marketing Surveillance Study. Sakata, Y., Matsuoka, T., Ohashi, S., et al.[2020]

References

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

Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. [2022]

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

Genetics and immunology: reinvigorated. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. [2023]

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

COM701 Shows Antitumor Activity, +/- Nivolumab. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the GREEN study. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Use of a Healthcare Claims Database for Post-Marketing Safety Assessments of Eribulin in Japan: A Comparative Assessment with a Prospective Post-Marketing Surveillance Study. [2020]