CD40 Agonist + PD-1 Inhibitor for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Pennsylvania
Must not be taking: Immunosuppressants
Disqualifiers: Hepatitis B/C, Autoimmune disease, others
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot use immunosuppressive medications within 14 days before starting the study treatment, except for certain low-dose steroids and local steroid treatments.
What data supports the effectiveness of the drug combination of CD40 Agonist and PD-1 Inhibitor for head and neck cancer?
Nivolumab, a PD-1 inhibitor, has shown better survival rates than standard chemotherapy for certain head and neck cancers, according to the CheckMate-141 trial.
12345What is known about the safety of PD-1 inhibitors like Nivolumab for head and neck cancer?
PD-1 inhibitors, such as Nivolumab, are generally safe but can cause side effects like diarrhea, skin rash, and thyroid issues. Rarely, they may lead to serious lung inflammation or other immune-related problems.
34678What makes the CD40 Agonist + PD-1 Inhibitor drug unique for head and neck cancer?
This drug combines a CD40 agonist, which helps activate the immune system, with a PD-1 inhibitor like nivolumab, which prevents cancer cells from hiding from the immune system, offering a novel approach by potentially enhancing the immune response against head and neck cancer.
13459Eligibility 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.
You are expected to live for at least 12 weeks.
You have signed a document that explains the study and have permission from a special group that makes sure the study is safe and fair.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Pre-Surgery Treatment
Participants receive a single administration of LVGN3616 or LVGN3616 and LVGN7409, followed by surgical resection
2 weeks
4 visits (in-person)
Post-Surgery Follow-up
Participants undergo guideline-based standard of care post-surgical adjuvant therapies and are monitored for safety and effectiveness
12 months
Quarterly visits (in-person)
Participant Groups
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
Loading ...
Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
References
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.
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.
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).
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.
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.
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).
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).
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.
Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. [2020]Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC.