Ivonescimab for Metastatic NSCLC (HARMONi-7 Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Summit Therapeutics
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Clinical study of ivonescimab for first-line treatment of metastatic NSCLC patients with high PD-L1. Evaluating overall survival and progression free survival.
How is the drug Ivonescimab different from other treatments for metastatic NSCLC?
Ivonescimab is unique because it is a bispecific antibody that targets both programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF), potentially offering a dual mechanism to fight cancer by enhancing the immune response and inhibiting blood vessel growth in tumors.
1231113What is known about the safety of Ivonescimab for human use?
Ivonescimab, like other PD-1/PD-L1 inhibitors, can cause immune-related side effects, which are generally manageable but may require treatment adjustments. In patients with existing autoimmune conditions, these side effects can be more pronounced, but they are often similar to those seen in other patients and rarely lead to stopping treatment permanently.
458912Do 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.
What data supports the effectiveness of the drug Ivonescimab for treating metastatic NSCLC?
Ivonescimab is a bispecific antibody targeting proteins involved in cancer growth, and a study (HARMONi-5) evaluated its safety and effectiveness as a first- or second-line treatment for advanced NSCLC. While specific results from this study are not provided, similar treatments targeting these proteins have shown improved survival in NSCLC patients.
3671013Eligibility Criteria
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.
I am 18 years old or older.
I am fully active or can carry out light work.
My lung cancer type was confirmed by lab tests.
My tumor shows high PD-L1 levels based on a specific test.
Exclusion Criteria
My lung cancer is confirmed by tests and needs first-line treatments.
I have received treatment for advanced lung cancer.
My cancer has a specific genetic change treatable by approved drugs.
I have brain metastases larger than 1.5 cm or need brain radiation soon.
I am on medication for an autoimmune or lung condition.
I haven't had major surgery or serious injury in the last 4 weeks.
I have had pneumonia treated with steroids or have a lung condition.
I have moderate to severe nerve damage in my hands or feet.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A - IvonescimabExperimental Treatment1 Intervention
Subject will receive ivonescimab as an IV injection
Group II: Arm B - PembrolizumabActive Control1 Intervention
Subject will receive pembrolizumab as an IV injection
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Summit Therapeutics Research CenterLos Angeles, CA
Summit Therapeutics Research CenterCerritos, CA
Summit Therapeutics Research CenterTamarac, FL
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Who is running the clinical trial?
Summit TherapeuticsLead Sponsor
References
Ipilimumab in non-small cell lung cancer and small-cell lung cancer: new knowledge on a new therapeutic strategy. [2018]Despite recent advances with new chemotherapeutic agents and target therapies, the prognosis of NSCLC remains poor. Recent results from clinical trials of immunotherapeutic agents, especially with immune checkpoint inhibitors, make this approach very exciting in NSCLC. Ipilimumab is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen 4 that is able to stimulate the antitumour immune response by promoting T-cell activation.
Recent Advances in Immunotherapy in Metastatic NSCLC. [2022]Non-small cell lung cancer (NSCLC) is one of most common malignancies and the leading cause of cancer deaths worldwide. Despite advances in targeted therapies, majority of NSCLC patients do not have targetable genomic alterations. Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and several breakthroughs in immunotherapies have led to rapid expansion of this new treatment modality in NSCLC with recent FDA approvals of programed death receptor-1 inhibitors, such as nivolumab and pembrolizumab. Here, we review promising immunotherapeutic approaches in metastatic NSCLC, including checkpoint inhibitors, agents with other mechanisms of action, and immunotherapy combinations with other drugs. With advent of immunotherapy, therapeutic options in metastatic NSCLC are rapidly expanding with the hope to further expand life expectancy in metastatic lung cancer.
Immunotherapy in previously treated non-small cell lung cancer (NSCLC). [2020]Treatment with immunotherapy has made a significant impact in the outcomes for those individuals diagnosed with metastatic non-small cell lung cancer (NSCLC) and its use is currently an established treatment modality. In light of recent advances in immunotherapy, improved survival, particularly for patients with stage IV NSCLC, has been reported with durable and prolonged responses in a subset of patients. Immune check point inhibitors, which include nivolumab, pembrolizumab, and atezolizumab, are standard treatment options in the salvage setting. Nivolumab and atezolizumab are approved for patients regardless of programmed death-ligand 1 (PD-L1) expression, whereas pembrolizumab requires tumor PD-L1 expression at the cut-off ≥1%. In this review, we will outline the clinical development of immunotherapy in previously treated NSCLC, current challenges and discuss novel treatment strategies.
Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. [2022]Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.
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. [2020]Programmed cell death protein-1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have remarkable clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the breakdown of immune escape causes a variety of immune-related adverse events (irAEs). With the increasing use of PD-1/PD-L1 inhibitors alone or in combination with other therapies, awareness and management of irAEs have become more important. We aimed to assess the incidence and nature of irAEs associated with PD-1 and PD-L1 inhibitors for NSCLC.
Pharmacodynamics of current and emerging PD-1 and PD-L1 inhibitors for the treatment of non-small cell lung cancer. [2020]Introduction: As of today, one of the cornerstones of NSCLC treatment is represented by Immune Checkpoint Inhibitors (ICI) treatment in the form of anti-PD-1/PD-L1 monoclonal antibodies. However, apart from currently approved, recommended and employed agents (nivolumab, pembrolizumab, atezolizumab, durvalumab), several new agents are currently under development and investigation both in monotherapy and in combinational settings.Areas covered: This paper aims to discuss both the current state of the art and the most interesting emerging PD-1 and PD-L1 inhibitors and their present and future role in metastatic NSCLC treatment.Expert opinion: Great scientific interest lies in combinational settings, involving both already developed FDA and EMA approved and not approved agents and anti-PD-1 and PD-L1 inhibitors, that will certainly provide data about pharmacodynamic and clinical properties of these associations, enhancing our understanding of ICIs and cancer immunotherapy. Moreover, new potential predictive biomarkers are much needed, especially considering the less decisive role of PD-L1 in treatment algorithms involving chemo-immune combinations and the current lack of other validated predictive biomarkers.
Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. [2022]Nivolumab improves disease control and survival in advanced NSCLC in patients with good performance status (PS), but there is limited data on its efficacy in patients with poor PS.
Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis. [2022]Although anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC.
Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. [2022]Immune checkpoint inhibitors have yielded significant treatment progress in non-small cell lung cancer (NSCLC), while some special adverse events (AEs) named immune-related adverse events (irAEs) were observed in clinical trials. We aimed to systematically assess the incidences of AEs in immunotherapy of NSCLC.
Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC. [2023]We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC.
Sugemalimab, a novel PD-L1 inhibitor for treatment of advanced or metastatic non-small cell lung cancer. [2023]Nearly two-thirds of patients with non-small cell lung cancer (NSCLC) have locally advanced or metastatic disease at the time of diagnosis, and many patients with early-stage disease will eventually experience metastatic recurrence. In the absence of a known driver alteration, treatment of metastatic NSCLC is limited to immunotherapy with or without cytotoxic chemotherapy. For most patients with locally advanced unresectable NSCLC, the standard of care involves concurrent chemoradiation followed by consolidative immunotherapy. Several immune checkpoint inhibitors have been developed and approved for NSCLC in both the metastatic and adjuvant settings. This review will discuss sugemalimab, a novel programmed cell death 1 ligand 1 (PD-L1) inhibitor, for the treatment of advanced NSCLC.
Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer. [2023]Immunotherapies, such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1) antibodies have been shown to improve overall and progression-free survival (PFS) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). However, not all patients derive a meaningful clinical benefit. Additionally, patients receiving anti-PD-1/PD-L1 therapy can experience immune-related adverse events (irAEs). Clinically significant irAEs may require temporary pause or discontinuation of treatment. Having a tool to identify patients who may not benefit and/or are at risk for developing severe irAEs from immunotherapy will aid in an informed decision-making process for the patients and their physicians.
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. [2023]This study (HARMONi-5) aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor) as first- or second-line monotherapy in patients with advanced immunotherapy-naive NSCLC.