Ivonescimab for Metastatic NSCLC

(HARMONi-7 Trial)

Recruiting at 98 trial locations

Overseen By Summit Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Summit Therapeutics

Disqualifiers: Small cell lung cancer, CNS metastases, Active autoimmune, 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: Unknown

Duration: 6 months

780 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ivonescimab, an experimental drug for individuals with metastatic non-small cell lung cancer (NSCLC) that exhibits high levels of PD-L1, a protein influencing cancer growth. The researchers aim to determine if ivonescimab extends patient survival and delays cancer progression compared to pembrolizumab. It suits those with advanced NSCLC who have not received prior treatment and have tumors with high PD-L1 levels. Participants will receive their treatment via IV injection. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ivonescimab, a treatment for advanced non-small cell lung cancer (NSCLC), is generally safe. Studies indicate that patients tolerate ivonescimab well, with manageable side effects. For example, a review found that serious side effects are rare and usually not severe. Additionally, a study on NSCLC patients with brain metastases reported positive safety results, noting that most side effects were mild to moderate.

While researchers continue to study ivonescimab, these findings suggest it is generally well-tolerated by patients. However, it is important to consider all options and consult healthcare providers when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ivonescimab is unique because it represents a novel approach for treating metastatic non-small cell lung cancer (NSCLC). Most treatments for this condition, like pembrolizumab, focus on blocking the PD-1/PD-L1 pathway to help the immune system fight cancer. However, ivonescimab combines this mechanism with an additional targeting of the VEGF pathway, which plays a crucial role in blood vessel formation. This dual-action mechanism could potentially improve treatment effectiveness by not only enhancing the immune response but also disrupting the tumor's blood supply. Researchers are excited about ivonescimab because it could offer a more comprehensive attack on cancer cells and their supportive environment, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for metastatic NSCLC?

Research shows that ivonescimab, which participants in this trial may receive, may effectively treat advanced non-small cell lung cancer (NSCLC), particularly in patients with high levels of the protein PD-L1. Studies have found that patients taking ivonescimab tend to live longer without their cancer worsening. For example, after 6 months, 54% of patients on ivonescimab experienced no cancer progression, compared to 25.4% of those not on the treatment. After 12 months, 34.7% of patients on ivonescimab remained progression-free, compared to only 8.3% without it. These results suggest that ivonescimab could be a promising option for improving outcomes in NSCLC patients. Another treatment option in this trial is pembrolizumab, which researchers will compare to ivonescimab to evaluate its effectiveness. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV NSCLC who haven't had systemic treatment for metastatic cancer. They should have a life expectancy of at least 3 months, be relatively active (ECOG score 0-1), and their tumors must show high PD-L1 expression. People with small cell lung carcinoma, other cancers within the last 3 years, severe autoimmune or lung diseases, recent serious infections or surgeries, significant neuropathy, or symptomatic brain metastases can't join.

Inclusion Criteria

My lung cancer has spread to other parts of my body.

I haven't had systemic treatment for advanced lung cancer.

Expected life expectancy ≥ 3 months

Exclusion Criteria

Concurrent enrollment in another clinical study, unless patient is enrolled in a non-interventional clinical study or is completing survival follow-up

My lung cancer is confirmed by tests and needs first-line treatments.

I have received treatment for advanced lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ivonescimab or pembrolizumab as an IV injection for the first-line treatment of metastatic NSCLC

6 months

Follow-up

Participants are monitored for overall survival and progression-free survival after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The study tests Ivonescimab injection as a first-line treatment against Pembrolizumab in patients with advanced NSCLC showing high PD-L1 levels. It aims to see which drug helps patients live longer without their disease getting worse.

How Is the Trial Designed?

Group I: Arm A - Ivonescimab Experimental Treatment 1 Intervention

Subject will receive ivonescimab as an IV injection

Group II: Arm B - Pembrolizumab Active Control 1 Intervention

Subject will receive pembrolizumab as an IV injection

Who Is Running the Clinical Trial?

Summit Therapeutics

Lead Sponsor

Trials

18

Recruited

4,500+

Published Research Related to This Trial

Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and while many patients lack targetable genomic alterations, recent advances in immunotherapy have shown promise in treating this type of cancer.

The FDA has approved programmed death receptor-1 inhibitors like nivolumab and pembrolizumab, which are part of a growing range of immunotherapeutic options aimed at improving life expectancy for patients with metastatic NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in Immunotherapy in Metastatic NSCLC. Bansal, P., Osman, D., Gan, GN., et al.[2022]

Ipilimumab, an immune checkpoint inhibitor, shows promise in treating non-small cell lung cancer (NSCLC) by enhancing the body's antitumor immune response through T-cell activation, as indicated by recent clinical trials.

Future research should focus on identifying biomarkers to better select patients who may benefit from ipilimumab and exploring its combination with other cancer treatments to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in non-small cell lung cancer and small-cell lung cancer: new knowledge on a new therapeutic strategy. Rijavec, E., Genova, C., Barletta, G., et al.[2018]

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 2a trial involving 43 patients with advanced squamous non-small cell lung cancer (NSCLC), the combination of avelumab and cetuximab with chemotherapy resulted in a 34.9% objective response rate, indicating notable antitumor activity.

While the treatment showed tolerable safety, with 88.4% of patients experiencing treatment-related adverse events, the overall response rate was not significantly better than existing standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC. Andric, Z., Gálffy, G., Cobo Dols, M., et al.[2023]

Immune Checkpoint Inhibitors (ICIs), particularly anti-PD-1/PD-L1 monoclonal antibodies, are key treatments for metastatic non-small cell lung cancer (NSCLC), with several agents like nivolumab and pembrolizumab already in use and more under development.

There is significant interest in exploring combination therapies involving both approved and experimental agents alongside ICIs, as well as the need for new predictive biomarkers to improve treatment strategies, especially in chemo-immune combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics of current and emerging PD-1 and PD-L1 inhibitors for the treatment of non-small cell lung cancer. Rocco, D., Malapelle, U., Del Re, M., et al.[2020]

In a study of 56 patients with advanced non-small-cell lung cancer (NSCLC) and concurrent autoimmune disease (AID) treated with PD-1 or PD-L1 inhibitors, 55% experienced an AID flare or immune-related adverse event (irAE), but most were manageable and did not lead to treatment discontinuation.

The overall response rate to PD-(L)1 therapy in this population was 22%, indicating that while there are risks, the treatment can still be effective for patients with NSCLC and AID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. Leonardi, GC., Gainor, JF., Altan, M., et al.[2022]

A study involving 132 patients with non-small cell lung cancer developed prediction models using radiomic and clinical features to identify those likely to benefit from anti-PD-1/PD-L1 therapy, achieving a high prediction accuracy with an AUC-ROC of 87%.

The radiomic model effectively predicted progression-free survival, indicating that imaging features can help select patients who may respond well to immunotherapy, potentially reducing the risk of unnecessary treatment and associated immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer. Schroeder, KE., Acharya, L., Mani, H., et al.[2023]

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., et al.[2022]

Immunotherapy has significantly improved survival rates for patients with metastatic non-small cell lung cancer (NSCLC), particularly in stage IV cases, with some patients experiencing durable responses.

Immune checkpoint inhibitors like nivolumab and atezolizumab are effective treatment options regardless of PD-L1 expression, while pembrolizumab requires a minimum level of PD-L1 expression to be used, highlighting the importance of biomarker testing in treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in previously treated non-small cell lung cancer (NSCLC). Leal, TA., Ramalingam, SS.[2020]

Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, demonstrated promising efficacy in treating advanced non-small cell lung cancer (NSCLC), with an overall response rate (ORR) of 39.8% and a disease control rate of 86.1% among 108 patients studied over a median follow-up of 10.4 months.

The treatment was generally well tolerated, with only 22.2% of patients experiencing grade 3 or higher treatment-related adverse events, and a very low rate of treatment discontinuation (0.9%) due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. Wang, L., Luo, Y., Ren, S., et al.[2023]

In a systematic review of 26 cohorts involving 8,452 patients with non-small cell lung cancer (NSCLC), the presence of immune-related adverse events (irAEs) was significantly associated with improved overall survival (OS) and progression-free survival (PFS) in patients receiving anti-PD-1 antibodies.

Patients who developed irAEs after PD-1 treatment had better objective response rates (ORRs) and disease control rates (DCRs), indicating that irAEs could serve as a predictive biomarker for positive treatment outcomes in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis. Zhao, Z., Wang, X., Qu, J., et al.[2022]

Sugemalimab, a new PD-L1 inhibitor, is being explored as a treatment option for advanced non-small cell lung cancer (NSCLC), which often presents as locally advanced or metastatic disease at diagnosis.

Current treatment for metastatic NSCLC primarily involves immunotherapy, sometimes combined with chemotherapy, highlighting the importance of novel therapies like sugemalimab in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugemalimab, a novel PD-L1 inhibitor for treatment of advanced or metastatic non-small cell lung cancer. Sakamoto, M., Jimeno, A.[2023]

In a meta-analysis of 16 clinical trials involving 6208 patients with non-small cell lung cancer, the overall incidence of immune-related adverse events (irAEs) was found to be 22%, with a higher rate of severe irAEs (4%) associated with PD-1 inhibitors compared to PD-L1 inhibitors.

The most common organ-specific irAEs occurred in the endocrine system, skin, pulmonary tract, and gastrointestinal tract, with pneumonitis being the leading cause of death among the 14 patients (0.34%) who died due to irAEs, highlighting the importance of monitoring and managing these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis. Sun, X., Roudi, R., Dai, T., et al.[2020]

Citations

1. smmttx.com smmttx.com/wp-content/uploads/2025/11/2025_PR_1107-SITC-HARMONi-A-Data-_-FINAL-v2.pdf

Ivonescimab Plus Chemotherapy Demonstrates a ... HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11818946/

Efficacy and Safety of Ivonescimab in the Treatment ... Ivonescimab showed promising antitumor activity and improved clinical outcomes, particularly in patients with higher PD-L1 expression levels and those ...

3. ascopost.com ascopost.com/issues/october-25-2025/improved-outcomes-reported-with-second-line-regimen-of-ivonescimab-plus-chemotherapy-in-nsclc/

Improved Outcomes Reported With Second-Line Regimen ... The progression-free survival rate at 6 months was 54.0% with ivonescimab vs 25.4% without it, and at 12 months, the rate was 34.7% vs 8.3%, ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8664

A randomized phase 3 study of ivonescimab plus ... In a phase 2 trial, ivonescimab plus chemotherapy showed objective response rates (ORRs) of 71.4% and 54.2% and median progression-free survival ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05899608

NCT05899608 | Clinical Study of Ivonescimab for First-line ... The primary endpoint is overall survival and progression free survival assessed by investigator. The key secondary endpoints include response and safety.

6. smmttx.com smmttx.com/pressrelease/promising-intracranial-anti-tumor-activity-and-safety-data-for-ivonescimab-in-nsclc-patients-with-brain-metastases-featured-at-elcc-2024/

Promising Intracranial Anti-Tumor Activity and Safety Data ... Promising Intracranial Anti-Tumor Activity and Safety Data for Ivonescimab in NSCLC Patients with Brain Metastases Featured at ELCC 2024 ...

7. akesobio.com akesobio.com/en/media/akeso-news/240908/

WCLC 2024 | Akeso's Ivonescimab Head-to-Head Phase III ... Ivonescimab as first-line treatment for PD-L1 positive NSCLC significantly extends median progression-free survival (mPFS) compared to pembrolizumab.