ABBV-011 + Budigalimab for Small Cell Lung Cancer

Recruiting at 35 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: Immunosuppressives, Live vaccines

Disqualifiers: Liver cirrhosis, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

132 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, ABBV-011, alone and with budigalimab, in patients whose small cell lung cancer has returned or didn't respond to treatment. ABBV-011 aims to kill cancer cells directly, and budigalimab boosts the immune system to fight the cancer.

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, you must have stopped any prior anticancer therapy at least 4 weeks before starting the study drug.

What data supports the effectiveness of the drug ABBV-011 + Budigalimab for Small Cell Lung Cancer?

Research shows that combining drugs targeting PD-1, like budigalimab, with other treatments can enhance antitumor activity in small cell lung cancer. Additionally, combining different immune therapies has shown promising results in improving treatment outcomes for this type of cancer. ^{1 2 3 4 5}

What safety data exists for ABBV-011 and Budigalimab in humans?

The research articles discuss immune-related adverse events (side effects related to the immune system) associated with immune checkpoint inhibitors, which are similar types of treatments to Budigalimab. These side effects can include lung issues and colitis (inflammation of the colon), highlighting the importance of monitoring and managing these reactions. ^{6 7 8 9 10}

How is the drug combination of ABBV-011 and Budigalimab unique for treating small cell lung cancer?

The drug combination of ABBV-011 and Budigalimab is unique because it targets both PD-1, a protein that helps cancer cells evade the immune system, and potentially other cancer-specific targets, which may enhance antitumor activity compared to existing treatments that focus on single targets. ^{1 3 11 12 13}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with small cell lung cancer that's come back or hasn't responded to treatment. They should have had no more than three prior therapies and can't be eligible for curative treatments. Participants need a certain level of health, including organ function, and an expected lifespan of at least 12 weeks. They must not have serious heart conditions, liver issues like cirrhosis, or a history of severe drug reactions.

Inclusion Criteria

I have recovered from major side effects of previous treatments, except for hair loss.

My small cell lung cancer tissue tests positive for a specific target.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

Participants with a history of hypersensitivity to the active ingredients or any excipients of study drugs (ABBV-011 or budigalimab [ABBV-181]) will be excluded

You have had a severe skin reaction to a medication in the past.

I have a history of liver issues or alcohol dependence.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Single-agent ABBV-011 dose regimen finding cohort

Until maximum tolerated dose is declared

Treatment Part B

Single-agent ABBV-011 dose expansion cohort

Until completion of dose expansion

Treatment Part C

ABBV-011 and budigalimab (ABBV-181) combination escalation and expansion cohort

Until completion of combination escalation and expansion

Treatment Part D

Single-agent ABBV-011 dose-evaluating cohort for Japan

Every 3 weeks (Q3wk), on Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• ABBV-011
• Budigalimab

Trial Overview The study tests ABBV-011 alone and combined with Budigalimab in people whose lung cancer has relapsed or is resistant to treatment. It includes dose-finding and expansion phases for both the single agent (ABBV-011) and the combination therapy with Budigalimab.

Participant Groups

Group I: Part D: ABBV-011 Dose Evaluation for Japan Experimental Treatment 1 Intervention

ABBV-011 via intravenous administration will be administered every 3 weeks (Q3wk), on Day 1 of each 21-day cycle or alternate dosing regimens.

Group II: Part C: ABBV-011 + Budigalimab Escalation and Expansion Experimental Treatment 2 Interventions

ABBV-011 via intravenous administration at various doses and dosing regimens starting at least 1 dose level below the recommended single-agent dose of ABBV-011 for Part B plus Budigalimab via intravenous administration at fixed doses and various dosing regimens.

Group III: Part B: ABBV-011 Dose Expansion Experimental Treatment 1 Intervention

ABBV-011 via intravenous administration at dose regimen(s) that will not exceed the maximum tolerated dose determined in Part A.

Group IV: Part A: ABBV-011 Dose Escalation Experimental Treatment 1 Intervention

ABBV-011 via intravenous administration at various doses and dosing regimens until the maximum tolerated dose and/or the recommended Part B dose(s) is declared.

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

Findings from Research

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

Combining immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 with chemotherapy significantly improves overall survival and progression-free survival in small cell lung cancer patients, with hazard ratios of 0.83 and 0.80, respectively, based on a review of five studies.

The combination treatment does not increase the rate of severe adverse events compared to conventional chemotherapy, indicating that it is a tolerable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. Wu, J., Zhang, A., Li, L., et al.[2021]

In a phase I study involving 40 patients with extensive-stage small cell lung cancer (SCLC), the combination of quavonlimab and pembrolizumab showed encouraging antitumor activity with an objective response rate (ORR) of 18%, indicating potential effectiveness in treating this aggressive cancer.

The treatment was generally well tolerated, with 80% of patients experiencing treatment-related adverse events, but only 10% facing dose-limiting toxicity, suggesting that the combination therapy has manageable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. Cho, BC., Yoh, K., Perets, R., et al.[2021]

A total of 9202 adverse pulmonary events related to immune checkpoint inhibitors were identified, with common issues including pneumonitis, interstitial lung disease, and respiratory failure, indicating significant pulmonary toxicity associated with these treatments.

Most pulmonary immune-related adverse events were severe and contributed to a notable number of fatalities, suggesting that the risks of using immune checkpoint inhibitors may be underrecognized in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy. Reese, SW., Cone, E., Marchese, M., et al.[2021]

In a review of 52 randomized controlled trials involving 23,322 patients with non-small cell lung cancer (NSCLC), the incidence of serious adverse events (AEs) was found to be similar between immune monotherapy and chemotherapy, with serious AEs occurring in about 33-48% of patients depending on the treatment type.

Certain immune-related adverse events (irAEs), such as colitis, pneumonitis, and rash, were more common in immunotherapy groups compared to chemotherapy, and interestingly, the occurrence of serious AEs like hepatitis and pneumonitis was positively correlated with better progression-free survival in patients receiving PD1 and PDL1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. Zhou, C., Li, M., Wang, Z., et al.[2022]

Monoclonal antibodies like nivolumab and pembrolizumab, which target PD-1, have shown a survival benefit and better tolerability compared to standard second-line chemotherapy in non-small cell lung cancer, as demonstrated in three phase III trials.

Patients receiving PD-1 inhibitors may experience unique immune-related adverse events that require early recognition and a multidisciplinary management approach, highlighting the need for ongoing education among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. O'Kane, GM., Labbé, C., Doherty, MK., et al.[2018]

References

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

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The evolving landscape of immunotherapy in small-cell lung cancer: A focus on predictive biomarkers. [2019]

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

Combined VEGF and PD-L1 Blockade Displays Synergistic Treatment Effects in an Autochthonous Mouse Model of Small Cell Lung Cancer. [2019]

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

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. [2021]

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

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-mediated colitis in a patient with epidermoid metastatic lung cancer: new and emerging toxicities. [2023]

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

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. [2020]

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

In search of lost biomarker for immunotherapy in small-cell lung cancer. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Camrelizumab plus platinum-irinotecan followed by maintenance camrelizumab plus apatinib in untreated extensive-stage small-cell lung cancer: a nonrandomized clinical trial. [2023]

13. Ireland pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade in small cell lung cancer. [2020]