Acasunlimab + Pembrolizumab for Lung Cancer

Not currently recruiting at 56 trial locations

Overseen By Genmab A/S Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genmab

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: EGFR mutations, Pneumonitis, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new drug, acasunlimab, for treating non-small cell lung cancer that has either recurred after treatment or not responded to it. Researchers aim to compare the effectiveness of acasunlimab alone versus in combination with pembrolizumab, a drug already used for cancer. The trial consists of two parts: the first assesses safety and optimal doses, while the second evaluates treatment efficacy. Individuals with stage 4 non-small cell lung cancer, who have previously tried other treatments without success, may be suitable candidates for this study. Participants will receive active treatment and be randomly assigned to different doses and combinations of drugs. As a Phase 2 trial, this research focuses on measuring treatment effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer agents at least 28 days before starting acasunlimab. If you are on chronic systemic immunosuppressive corticosteroids, you may need to adjust your dosage. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research shows that acasunlimab, also known as GEN1046, is generally well-tolerated when used alone or with pembrolizumab. In earlier studies, patients receiving both treatments had a 12-month survival rate of 69% and lived an average of 17.5 months. This suggests the treatment can be effective without causing severe side effects.

When used alone, acasunlimab helps the immune system fight cancer. Combined with pembrolizumab, this effect appears stronger, though monitoring for side effects remains important. Similar studies report common side effects like tiredness and nausea, which are usually manageable.

This is a Phase 2 trial, indicating the treatment has passed initial safety tests. It is now being tested on more people to better understand its effects and side effects. This should provide participants with some confidence in the treatment's safety. However, healthcare professionals will closely monitor participants to ensure their safety and well-being. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because acasunlimab offers a fresh approach to tackling lung cancer. Unlike traditional chemotherapy and targeted therapies, acasunlimab is a novel immunotherapy that works by enhancing the body's immune response to fight cancer cells more effectively. When combined with pembrolizumab, a well-known checkpoint inhibitor, it might offer a powerful synergistic effect, potentially leading to improved outcomes for patients. This combination is administered in varying schedules, which could optimize the treatment's effectiveness and reduce side effects, making it a promising option compared to current treatments.

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

Previous studies have shown promising results for acasunlimab in treating non-small cell lung cancer (NSCLC). One study found that 69% of patients were still alive after 12 months, with an average survival time of 17.5 months. In this trial, participants will receive acasunlimab alone or in combination with pembrolizumab. Past studies demonstrated that combining acasunlimab with pembrolizumab extended patient survival and provided more lasting responses compared to acasunlimab alone. This combination treatment generally resulted in manageable side effects, meaning they weren't too severe. These findings suggest that both acasunlimab alone and with pembrolizumab could be effective for patients whose NSCLC has returned or hasn't responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

Adults with stage 4 non-small cell lung cancer who've had prior treatment including anti-PD-1/PD-L1 antibodies can join this trial. They should be relatively active (ECOG ≤1), have a life expectancy of at least 3 months, and tumors expressing PD-L1 in ≥1% of cells. Excluded are those with recent radiation or immunotherapy side effects, severe heart conditions, uncontrolled hypertension, certain genetic mutations unless previously treated for them, significant autoimmune disease risk, liver disease, organ transplants within the last 3 months or known allergies to trial drugs.

Inclusion Criteria

I have stage 4 NSCLC and was treated with an anti-PD-1/PD-L1 drug.

You are expected to live for at least 3 more months.

My organs and bone marrow are functioning well.

Exclusion Criteria

I have not used experimental drugs for stage 4 lung cancer.

I do not have severe heart failure, unstable chest pain, or irregular heartbeats.

I haven't taken high doses of steroids like prednisone before starting the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acasunlimab alone or in combination with pembrolizumab, with dosing every 3 or 6 weeks depending on the treatment arm

6 months

Weekly visits initially, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• GEN1046
• Pembrolizumab

Trial Overview The trial is testing acasunlimab alone and combined with pembrolizumab in patients whose lung cancer has worsened after standard care. It aims to see how safe these treatments are and how well they work against the cancer.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 2 Interventions

Treatment with acasunlimab + pembrolizumab once every 42 days

Group II: Arm B Experimental Treatment 2 Interventions

Treatment with acasunlimab + pembrolizumab once every 21 days

Group III: Arm A Experimental Treatment 1 Intervention

Treatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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 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]

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-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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 study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

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]

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 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In the phase Ib KEYNOTE-001 study, pembrolizumab monotherapy showed durable antitumor activity in advanced non-small-cell lung cancer (NSCLC), with a median overall survival (OS) of 22.3 months for treatment-naive patients and 10.5 months for previously treated patients, and 5-year OS rates of 23.2% and 15.5%, respectively.

Patients with a PD-L1 tumor proportion score of 50% or greater had even better outcomes, with 5-year OS rates of 29.6% for treatment-naive and 25.0% for previously treated patients, while the treatment maintained a favorable safety profile with minimal late-onset adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. Garon, EB., Hellmann, MD., Rizvi, NA., et al.[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 patients with non-small cell lung cancer (NSCLC), platinum-based chemotherapy significantly increased the presence of NSCLC-specific antibodies and various immune markers in the blood, indicating an immune response to the treatment.

Immune checkpoint inhibitors (ICIs) like Nivolumab and Pembrolizumab also altered the immune profile, enhancing certain T-cell and B-cell markers, which suggests that both chemotherapy and ICIs can modify the immune landscape in advanced NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy. Neuperger, P., Szalontai, K., Gémes, N., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05117242

NCT05117242 | Safety and Efficacy Study of GEN1046 as ... 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 ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/genmab-data-phase-ii-gct1046/

Genmab report data from Phase II GCT1046-04 trial ... The trial showed an overall survival rate of 69% over 12 months, a median overall survival of 17.5 months, and an overall response rate of 30% ...

3. 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 ... The results showed a 12-month overall survival (“OS”) rate of 69%, a median overall survival (“mOS”) of 17.5 months, and a 30% overall response ...

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

Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in ... Conclusions: In PD-L1+ pts with mNSCLC following progression on prior CPI tx, acasunlimab + pembro combo showed a manageable safety profile and ...

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/NCT03917381

Study Details | NCT03917381 | GEN1046 Safety Trial in ... The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together ...