Acasunlimab + Pembrolizumab for Lung Cancer

Recruiting at 280 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genmab

Must be taking: PD-1/PD-L1 inhibitors, Platinum chemotherapy

Must not be taking: Docetaxel, 4-1BB agents

Disqualifiers: EGFR, ALK, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

702 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with metastatic non-small cell lung cancer (NSCLC). The researchers aim to determine if acasunlimab (an experimental treatment) combined with pembrolizumab is more effective than the standard treatment, docetaxel. The trial seeks participants who have previously received certain therapies but whose cancer has progressed. Those with lung cancer exhibiting tumor PD-L1 positivity, who have tried other unsuccessful treatments, may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, providing access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you have not taken any anticancer agent within 28 days before starting the trial treatment. Other specific medication requirements are not detailed in the provided information.

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

Research has shown that combining acasunlimab and pembrolizumab yields promising safety results. Initial findings suggest most people tolerate this treatment well. For instance, an ongoing study found that 69% of participants were still alive after 12 months, indicating the treatment's potential. However, like any treatment, side effects can occur. The studies aim to determine the best doses to ensure both efficacy and safety. Pembrolizumab is already approved for other uses, so its safety profile is generally well-known.

This trial is in a later stage, indicating existing evidence supports the treatments' safety for larger groups. However, each person's experience may vary. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Acasunlimab combined with Pembrolizumab for lung cancer because this duo offers a novel approach by leveraging the immune system to fight cancer more effectively. Unlike traditional chemotherapy drugs like Docetaxel, which attack rapidly dividing cells indiscriminately, Pembrolizumab is an immune checkpoint inhibitor that helps the immune cells recognize and attack cancer cells. Acasunlimab may enhance this effect by further modulating the immune response. This combination has the potential to provide a more targeted treatment with fewer side effects and improved outcomes for patients.

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

In this trial, participants in Arm A will receive a combination of acasunlimab and pembrolizumab. Research shows this combination may help treat non-small cell lung cancer (NSCLC). Early studies indicated that 69% of patients were alive after 12 months, with an average survival time of 17.5 months for those on this treatment. Acasunlimab aids the immune system in attacking cancer by targeting proteins that allow tumors to evade immune cells. When combined with pembrolizumab, a well-known cancer treatment, this effect strengthens. Although more research is needed, these early results suggest this combination could be effective for people with this type of lung cancer. Participants in Arm B will receive docetaxel, serving as the active comparator in this trial. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

This trial is for people with PD-L1-positive metastatic non-small cell lung cancer who have already tried treatments with PD-1/PD-L1 inhibitors and platinum-based chemotherapy. It's not suitable for those who can't take docetaxel or have had certain previous treatments that the study excludes.

Inclusion Criteria

Participant has measurable disease according to RECIST v1.1 as assessed by the investigator at baseline

Participant has a life expectancy of ≥3 months

My recent tests show my organs and bone marrow are functioning well.

Exclusion Criteria

I have new or worsening brain metastases or a history of cancer in my brain's lining.

My cancer has specific mutations and I can't get targeted therapies.

I have been treated with docetaxel for lung cancer.

Timeline for a Trial Participant

Pre-screening

Optional pre-screening period to assess initial eligibility

8 weeks

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either Acasunlimab and Pembrolizumab every 6 weeks or Docetaxel every 3 weeks

Up to 2 years

Every 3-6 weeks (in-person)

Safety Follow-up

Participants are monitored for safety after treatment completion

13 weeks

Post-treatment Follow-up

Participants are monitored for long-term outcomes and survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Acasunlimab
• Docetaxel
• Pembrolizumab

Trial Overview The trial compares a new combination of drugs, Acasunlimab and Pembrolizumab, against the standard treatment, Docetaxel. Participants are randomly assigned to one of these treatments to see if the new combo is more effective.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).

Group II: Arm B Active Control 1 Intervention

Docetaxel, 75 mg/m\^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Published Research Related to This Trial

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a phase Ib study involving 64 patients with Stage IV non-small cell lung cancer (NSCLC), the combination of necitumumab and pembrolizumab showed a confirmed overall response rate of 23.4%, indicating modest efficacy in this patient population.

The treatment was well-tolerated, with no dose-limiting toxicities reported, and the safety profile was consistent with typical effects of epidermal growth factor receptor inhibitors and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. Besse, B., Garrido, P., Cortot, AB., et al.[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]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2533

Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in ... Acasunlimab is a bispecific antibody designed to elicit antitumor immune response via conditional 4-1BB activation strictly dependent on simultaneous PD-L1 ...

2. investors.biontech.de investors.biontech.de/news-releases/news-release-details/investigational-acasunlimab-duobodyr-pd-l1x4-1bb-combination

Investigational Acasunlimab (DuoBody® -PD-L1x4-1BB) in ... Initial data from the ongoing Phase 2 trial showed a 12-month overall survival rate of 69% and a median overall survival of 17.5 months in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06635824

NCT06635824 | Trial to Evaluate Acasunlimab and ... Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11987116/

Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody ... Consistent with the strong preclinical evidence presented here, the combination of acasunlimab and pembrolizumab demonstrated improved ...

5. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=GCT1046-04

Safety and Efficacy Study of GEN1046 as a Single Agent or ... The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05117242

NCT05117242 | Safety and Efficacy Study of GEN1046 as ... This trial has 2 parts. The purpose of the first part is to find out if the combination of acasunlimab and pembrolizumab is safe and to find out the best doses ...