ABBV-011 + Budigalimab for Small Cell Lung Cancer

No longer recruiting at 45 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ABBV-011, both alone and in combination with budigalimab (also known as ABBV-181), to determine their effectiveness in treating small cell lung cancer (SCLC) that hasn't responded to previous treatments. The trial aims to find the right dose and assess the combination's efficacy. It is designed for individuals with SCLC who have undergone at least one unsuccessful round of chemotherapy and have measurable tumors. Participants should not have serious liver, heart, or lung conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In earlier studies, ABBV-011 was generally well tolerated by patients. They received doses up to 1.0 mg/kg every three weeks, and researchers did not find a dose that was too high, indicating safety at these levels. Participants also showed positive responses to the treatment.

When combined with budigalimab, patients with small cell lung cancer tolerated the combination well. This suggests that adding budigalimab does not significantly increase side effects.

Overall, both ABBV-011 alone and with budigalimab appear safe based on early findings. However, as this is a Phase 1 trial, more studies are needed to fully understand the safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for small cell lung cancer, which often include chemotherapy and immunotherapy, ABBV-011 and Budigalimab offer a novel approach. ABBV-011 is an antibody-drug conjugate, meaning it specifically targets cancer cells with a payload designed to kill them, potentially reducing the impact on healthy cells. Budigalimab, on the other hand, is an anti-PD-1 antibody that may help the immune system better recognize and attack cancer cells. Researchers are excited about these treatments because they represent a potential shift towards more targeted and personalized therapies, which could improve outcomes and reduce side effects compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that ABBV-011 could effectively treat small cell lung cancer. In earlier studies, patients generally tolerated it well, and it showed promise in slowing cancer progression. On average, patients lived for 3.5 months without their cancer worsening. Specifically, one study found that 54% of patients did not experience cancer progression for at least 3 months, indicating early positive effects.

This trial tests ABBV-011 both alone and with another drug, Budigalimab. When combined with Budigalimab, ABBV-011 might work even better. Budigalimab has also shown good results in similar situations and is generally well tolerated. Together, these treatments are being tested to help patients whose small cell lung cancer has returned or not responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3002

First-in-human study of ABBV-011, a seizure-related ... The median progression-free survival was 3.5 months. Conclusions: The MTD was not reached and ABBV-011 was well tolerated at 1.0 mg/kg with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39287821/

A Phase I First-in-Human Study of ABBV-011, a ... - PubMed Conclusions: ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/30/22/5042/749566/A-Phase-I-First-in-Human-Study-of-ABBV-011-a

A Phase I First-in-Human Study of ABBV-011, a Seizure ... Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine neoplasm with a dismal 5-year survival rate of 6.8%. There is a high unmet need for novel ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03639194

NCT03639194 | A Study of ABBV-011 Alone and in ... The study consists of 4 parts: Part A is a single-agent ABBV-011 dose regimen finding cohort; followed by Part B, a single-agent ABBV-011 dose expansion cohort; ...

5. onclive.com onclive.com/view/abbv-011-showcases-early-tolerability-antitumor-activity-in-small-cell-lung-cancer

ABBV-011 Showcases Early Tolerability, Antitumor Activity ... Additional efficacy data showed that in all 40 patients in the 1-mg/kg cohort, the 3-month estimated PFS rate was 54% (95% CI, 37%-68%); the 6- ...