Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: Autoimmune disease, HIV, Hepatitis B/C, others
No Placebo Group
Prior Safety Data
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?To learn if ivonescimab can help to control advanced cSCC. The safety and effects of ivonescimab will also be studied.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, there is a requirement for a 'washout period' (time without taking certain medications) from previous therapies before starting the study treatment.
What data supports the effectiveness of the drug Ivonescimab for skin cancer?
Ivonescimab has shown safety and effectiveness as a treatment for advanced non-small cell lung cancer (NSCLC) in patients who have not previously received immunotherapy, suggesting potential benefits for other cancers like skin cancer.
12345What is known about the safety of Ivonescimab and similar treatments?
Ivonescimab, also known as AK-112 or Evoximab, is a type of immune checkpoint inhibitor, which can cause skin-related side effects like rashes, itching, and vitiligo (loss of skin color in patches). These side effects are common with similar treatments and are generally considered manageable.
678910What makes the drug Ivonescimab unique for treating skin cancer?
Ivonescimab is unique because it is a bispecific antibody that targets both PD-1 (a protein that helps cancer cells evade the immune system) and VEGF (a protein that promotes blood vessel growth in tumors), potentially enhancing the immune response against skin cancer.
35111213Eligibility Criteria
This trial is for adults over 18 with advanced skin cancer (cSCC) that can't be removed or has spread, and who didn't respond to anti-PD-1 therapy. They should have a life expectancy of at least 3 months, manageable blood pressure on up to one medication, and agree to use contraception. People with certain medical conditions, previous severe reactions to PD-1 inhibitors, active infections requiring IV antibiotics, or uncontrolled illnesses are excluded.Inclusion Criteria
I am fully active or can carry out light work.
My blood pressure is controlled with up to one medication.
I am 18 years old or older.
My skin cancer cannot be removed with surgery and may have spread.
I have completed all previous cancer treatments before starting this study.
My condition did not improve after anti-PD-1 therapy.
Exclusion Criteria
I had to stop or pause PD-1 inhibitor treatment due to side effects.
I have a history of hepatitis B or C.
I have had a transplant of an organ or stem cells from a donor.
I do not have an active infection needing IV antibiotics or any severe illness requiring hospitalization.
I have tested positive for HIV/AIDS.
I have not received a live vaccine in the last 4 weeks.
Participant Groups
The study tests ivonescimab's ability to control advanced cutaneous Squamous Cell Carcinoma (cSCC). It will assess the safety and effects of this drug in patients who haven't responded well to other treatments like anti-PD-1 therapy.
1Treatment groups
Experimental Treatment
Group I: IvonescimabExperimental Treatment1 Intervention
Participants found to be eligible to take part in this study, you will receive ivonescimab by vein over about 1-2 hours on Day 1 of each 21-day cycle (1 time every 3 weeks).
Ivonescimab is already approved in China for the following indications:
🇨🇳 Approved in China as Ivonescimab for:
- Locally advanced or metastatic non-squamous NSCLC
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
Summit TherapeuticsIndustry Sponsor
References
First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors. [2023]Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in antiangiogenesis which has been an essential strategy for cancer treatment. We report the first-in-human study of AK109, a novel anti-VEGFR2 monoclonal antibody, to characterize the safety profile and pharmacokinetics/pharmacodynamics (PK/PD) properties, and explore the preliminary antitumor efficacy in patients with solid tumors.
First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). [2023]The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors.
A phase 2 randomised study of ramucirumab (IMC-1121B) with or without dacarbazine in patients with metastatic melanoma. [2023]To evaluate the efficacy and safety of ramucirumab (IMC-1121B; LY3009806), a fully human monoclonal antibody targeting the vascular endothelial growth factor receptor-2, alone and in combination with dacarbazine in chemotherapy-naïve patients with metastatic melanoma (MM).
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.
Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. [2021]IMC-18F1 (icrucumab), a human monoclonal antibody against vascular endothelial growth factor receptor-1 (VEGFR-1), potently inhibits ligand-dependent phosphorylation of VEGFR-1 and downstream signaling, making icrucumab an attractive candidate for antitumor activity.
Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. [2023]Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.
Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy. [2022]Immunotherapy has experienced impressive progress in cancer treatment. Antibodies against PD-1 improved survival in different types of cancer including melanoma. They are generally well tolerated. However, skin toxicities including pruritus, rashes, and vitiligo are reported. Although frequent, they have not been characterized further yet. In this analysis, we aimed to systematically assess and characterize the adverse cutaneous reactions observed in patients with melanoma treated with anti-PD-1 antibodies.
Integrated Safety Analysis on Skin Cancers among Patients with Psoriasis Receiving Ixekizumab in Clinical Trials. [2023]Limited data exist on skin cancer risk in patients with psoriasis using biologics. Here, we report treatment-emergent adverse events (TEAEs) of skin cancer in patients treated with ixekizumab from psoriasis clinical trials.
Side effects of systemic oncological therapies in dermatology. [2012]The discovery of specific gene mutations, termed "driver mutations", in different tumors has brought personalized medicine into the focus of cancer treatment. Targeted treatment agents generally are administered orally and have a tolerable adverse event profile; they have become widely used in both inpatient and outpatient settings. The approval of the selective BRAF inhibitor vemurafenib (Zelboraf®) as first-line therapy of metastatic melanoma in Europe in February 2012 as well as the increasing use of MEK inhibitors within clinical trials confronts dermatologists and oncologists with a new spectrum of side effects. Knowledge of these possible adverse events and their management will be crucial for optimized patient care. This article offers an overview of the most important adverse events of currently employed dermato-oncologic therapeutic agents.
Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors. [2021]The advent of Immune Checkpoint Inhibitors (ICIs) as a standard of care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at the same time the attention on some safety issues related to their use. To assess the incidence of psoriasis as a specific immune-related cutaneous adverse event attributing to ICIs using the Eudravigilance reporting system. All reports of adverse drug reactions (ADRs) concerning either exacerbation of psoriasis or de novo onset of psoriasis/psoriasiform reactions associated to the use of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab and tremelimumab, and the Programmed cell Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab were identified and extracted from the Eudravigilance reporting system, during the period between the date of market licensing (for each study drug) and 30 October 2020. 8213 reports of cutaneous ADRs associated with at least one of study drug have been recorded, of which 315 (3.8%) reporting psoriasis and/or psoriasiform reactions as ADR. In 70.8% of reports patients had pre-existing disease. ICIs-related skin toxicity is a well-established phenomenon, presenting with several conditions, sustained by an immune background based on the activity of some cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, and plasmocytes), inflammatory mediators, chemokines, and tumor-specific antibodies. In this setting, psoriasis represents probably the most paradigmatic model of these reactions, thus requiring adequate recognition as no guidelines on management are now available.
AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial. [2023]Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma. [2020]Vascular endothelial growth factor (VEGF) is a proangiogenic molecule produced by melanoma cells. We hypothesized that administration of bevacizumab (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa-2b (IFN-alpha2b), an inhibitor of basic fibroblast growth factor (FGF), would lead to the regression of metastatic melanoma.
Erlotinib and bevacizumab have synergistic activity against melanoma. [2018]Melanoma is one of the most aggressive types of cancer with currently no chance of cure once the disease has spread to distant sites. Therapeutic options for advanced stage III and IV are very limited, mainly palliative, and show response in only approximately 20% of all cases. The presented preclinical study was done to investigate the influence of a combined treatment of the epidermal growth factor receptor inhibitor erlotinib and the vascular endothelial growth factor monoclonal antibody bevacizumab in melanoma.