CD40 Agonist + PD-1 Inhibitor for Head and Neck Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Pennsylvania
No Placebo Group
Trial Summary
What is the purpose of this trial?Prospective, open-label, phase 1 study of CD40 agonist (LVGN7409) and PD-1 inhibition (LVGN3616) in patients with resectable Human Papillomavirus (HPV)-negative mucosal head/neck squamous cell carcinoma (HNSCC). This protocol proposes to study the safety and immunological effects of LVGN7409, a CD40 agonistic antibody, when administered in combination with PD-1 inhibition prior to surgical resection.
Is the drug LVGN3616, LVGN7409 (also known as Nivolumab, Opdivo, LVGN7409, CD40 agonist) a promising treatment for head and neck cancer?Yes, the drug is promising because Nivolumab, one of its components, has shown better survival rates than standard chemotherapy for head and neck cancer. It targets the PD-1 pathway, which is a promising approach for treating this type of cancer.12345
What safety data is available for the CD40 Agonist + PD-1 Inhibitor treatment in head and neck cancer?The safety data for PD-1 inhibitors like nivolumab (Opdivo) and pembrolizumab, which are similar to the PD-1 inhibitor component of the treatment, indicate common side effects such as diarrhea, hypothyroidism, and skin rash, with rare severe cases like pneumonitis and tracheobronchial chondritis. Some patients may experience hyperprogression, where tumor growth accelerates. Specific safety data for the CD40 agonist (LVGN3616 or LVGN7409) in combination with PD-1 inhibitors is not detailed in the provided research.136810
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before the study treatment, except for certain types like intranasal, inhaled, or topical steroids, and low-dose systemic corticosteroids. It's best to discuss your specific medications with the study team.
What data supports the idea that CD40 Agonist + PD-1 Inhibitor for Head and Neck Cancer is an effective drug?The available research shows that Nivolumab, a part of the CD40 Agonist + PD-1 Inhibitor treatment, has been shown to improve survival rates compared to standard chemotherapy for head and neck cancer. Specifically, in a phase III clinical trial called CheckMate-141, Nivolumab was found to be more effective than the usual chemotherapy for patients with a certain type of head and neck cancer that is resistant to platinum-based treatments. However, it's important to note that not all patients benefit from this treatment, and some may even experience faster tumor growth.12379
Eligibility Criteria
Adults over 18 with HPV-negative squamous cell carcinoma in the head and neck area, who are not pregnant, can join this trial. They must weigh more than 30kg, have a life expectancy of at least 12 weeks, and agree to use effective contraception. Their cancer should be resectable (can be removed by surgery), they need to have a sample of their tumor available for study, and their major organs must function well.Inclusion Criteria
My body weight is more than 30kg.
I am 18 years old or older.
I have a non-FNA tumor tissue sample available for the study.
My blood, liver, and kidney functions are within normal ranges required for the study.
I am fully active or can carry out light work.
Treatment Details
The trial is testing LVGN7409 (a CD40 agonist) combined with LVGN3616 (a PD-1 inhibitor) on patients before they undergo surgical removal of their cancer. It's an early-phase study looking at how safe these drugs are together and what effects they have on the immune system.
2Treatment groups
Active Control
Group I: Arm A: PD1Active Control1 Intervention
Subjects in this arm will receive one dose of LVGN3616 (300mg).
Group II: Arm B: PD1 + CD40Active Control2 Interventions
Subjects in this arm will receive one dose of LVGN3616 (300mg) followed by one dose of CD40 LVGN7409 (1mg/kg).
LVGN3616 is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Classical Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
🇺🇸 Approved in United States as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Classical Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
🇨🇦 Approved in Canada as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Classical Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
🇯🇵 Approved in Japan as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Classical Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
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Who is running the clinical trial?
University of PennsylvaniaLead Sponsor
References
Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. [2022]Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK).
The genetic landscape of programmed death ligand-1 (PD-L1) alterations in head and neck cancer. [2021]Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets.
Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial.
Pembro Ups Survival in PD-L1-positive HNSCC. [2019]In a phase III trial, first-line treatment with single-agent pembrolizumab led to deep and durable responses among patients with head and neck tumors that expressed high levels of PD-L1.
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.
Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]Programmed death 1 (PD-1) blockade has changed the therapeutic landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with convincing overall response rates and overall survival benefits when compared to chemotherapy alone. The toxicity profile of pembrolizumab appears to be similar to that of other PD-1 or PD-L1 inhibitors, with frequent diarrhea, hypothyroidism or cutaneous rash cases, and rare cases of grade 3 to 5 pneumonitis.
Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. [2021]Nivolumab, an anti-PD-1 inhibitor, has demonstrated efficacy in patients with several types of recurrent and metastatic (R/M) squamous cell carcinoma of the head and neck. We evaluated patients with R/M-NPC receiving nivolumab.
Nivolumab-related tracheobronchial chondritis: Extremely rare manifestation of an immune-related adverse effect. [2021]Programmed death-1 checkpoint inhibitors, such as nivolumab, have successfully been utilized for recurrent or metastatic squamous cell carcinoma of the head and neck; however, their use may be associated with immune-related adverse effects (irAEs).
Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma. [2021]Immune checkpoint inhibitors are widely used in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We aimed to describe response rates to taxanes after progression on nivolumab in R/M HNSCC patients.
Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas. [2023]This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs).