Immunotherapy +/− Targeted Therapy for Nasopharyngeal Cancer
Recruiting in Palo Alto (17 mi)
+93 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Anticoagulants, Immunosuppressants
Disqualifiers: Autoimmune diseases, Active tumor bleeding, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests how well nivolumab and ipilimumab immunotherapy with or without cabozantinib works in treating patients with nasopharyngeal cancer that has come back (after a period of improvement) (recurrent), has spread from where it first started (primary site) to other places in the body (metastatic), or for which no treatment is currently available (incurable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving immunotherapy with nivolumab and ipilimumab and targeted therapy with cabozantinib may help shrink and stabilize nasopharyngeal cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it does prohibit certain medications like strong inhibitors or inducers of CYP3A4 and some anticoagulants. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination of Immunotherapy and Targeted Therapy for Nasopharyngeal Cancer?
While there is no direct data on the specific combination of Cabozantinib, Ipilimumab, and Nivolumab for nasopharyngeal cancer, similar treatments have shown promise. For example, Camrelizumab combined with apatinib, another immunotherapy and targeted therapy combination, showed promising results in patients with resistant nasopharyngeal cancer, with a significant portion of patients responding to the treatment.
12345Is the combination of immunotherapy and targeted therapy safe for nasopharyngeal cancer?
The combination of immunotherapy drugs like nivolumab and targeted therapies has shown a manageable safety profile in clinical trials for nasopharyngeal cancer. Common side effects include mild to moderate issues like high blood pressure and skin reactions, but serious side effects are less common. Overall, these treatments are generally considered safe for use in humans.
14678How is the drug combination of Cabozantinib S-malate, Ipilimumab, and Nivolumab unique for nasopharyngeal cancer?
This drug combination is unique because it combines immunotherapy (Ipilimumab and Nivolumab) with targeted therapy (Cabozantinib S-malate), which may offer a novel approach by enhancing the immune system's ability to fight cancer while also targeting specific cancer cell pathways, unlike traditional chemotherapy that is commonly used for nasopharyngeal cancer.
124910Eligibility Criteria
Adults (18+) with nasopharyngeal cancer that's returned, spread, or is incurable can join. They should have had no more than two prior treatments and not been on VEGFR targeted therapy. A good performance status (ECOG 0-2) and certain blood counts are required. The cancer must be measurable by scans or physical exam.Inclusion Criteria
My eligibility is not affected by my smoking history or specific cancer markers.
I haven't taken steroids or immunosuppressants in the last 14 days.
I have a tumor that can be measured and hasn't been treated with radiation.
+26 more
Exclusion Criteria
My tumor is not currently bleeding.
I haven't had any cancer except for skin cancer in the last 5 years.
I have a history of cancer.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nivolumab and ipilimumab with or without cabozantinib. Cycles repeat every 28 days for up to 2 years.
Up to 2 years
Monthly visits for treatment administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 8-12 weeks until disease progression or new therapy, then every 6 months for up to 2 years.
Up to 2 years
Regular follow-up visits every 8-12 weeks, then every 6 months
Participant Groups
The trial tests nivolumab and ipilimumab immunotherapy combined with cabozantinib against the same immunotherapy without cabozantinib to see if it helps control nasopharyngeal cancer better. These drugs may boost the immune system to fight cancer and block proteins that help cancer grow.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (nivolumab, ipilimumab, cabozantinib)Experimental Treatment6 Interventions
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial.
Group II: Arm A (nivolumab, ipilimumab)Active Control5 Interventions
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial.
Cabozantinib S-malate is already approved in United States, United States, European Union for the following indications:
🇺🇸 Approved in United States as Cabometyx for:
- Advanced renal cell carcinoma (RCC)
- Hepatocellular carcinoma (HCC)
- Locally advanced or metastatic differentiated thyroid cancer (DTC)
🇺🇸 Approved in United States as Cometriq for:
- Medullary thyroid cancer
🇪🇺 Approved in European Union as Cabometyx for:
- Advanced renal cell carcinoma (RCC)
- Hepatocellular carcinoma (HCC)
- Locally advanced or metastatic differentiated thyroid cancer (DTC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Kootenai Clinic Cancer Services - SandpointSandpoint, ID
Saint Alphonsus Cancer Care Center-OntarioOntario, OR
Ingalls Memorial HospitalHarvey, IL
University of IllinoisChicago, IL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. [2022]Platinum-based doublet chemotherapy regimens, preferentially gemcitabine plus cisplatin, are generally considered the first-line standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma. However, no consensus has been reached regarding treatment following progression after first-line therapy. Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody. We present safety and preliminary antitumour activity of camrelizumab alone as second-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma and combined with gemcitabine and cisplatin as first-line therapy in this patient population.
Nimotuzumab plus platinum-based chemotherapy versus platinum-based chemotherapy alone in patients with recurrent or metastatic nasopharyngeal carcinoma. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Palliative chemotherapy has been the mainstay treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, little is known about the efficacy and toxicity of nimotuzumab (NTZ) - a monoclonal antibody drug targeting epidermal growth factor receptor - plus chemotherapy (CT) versus CT alone for these patients.
Nimotuzumab, an Anti-EGFR Monoclonal Antibody, in the Treatment of Nasopharyngeal Carcinoma. [2021]Epidermal growth factor receptor (EGFR) is highly expressed in most of Nasopharyngeal carcinoma (NPC) samples and is associated with poor outcomes. Therefore, targeting EGFR may be a promising strategy to improve patient prognosis. Nimotuzumab is a humanized anti-EGFR monoclonal antibody. Recently, accumulating evidence has demonstrated that combination nimotuzumab and induction chemotherapy, radiotherapy, or concurrent chemoradiotherapy confer benefits for patients with NPC. Moreover, the side effects of such regimes are tolerable. In this review, we focus on the current data of nimotuzumab in clinical trials in the treatment of NPC.
Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial. [2023]Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.
Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. [2022]To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma.
Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials. [2020]Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1-5/3-5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1-5 AEs whereas camrelizumab and nivolumab regarding grade 3-5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1-positive and PD-L1-negative patients, respectively (P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.
Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study. [2023]Purpose Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has shown promising efficacy against several solid cancers, but evidence of its efficacy against relapsed and refractory nasopharyngeal carcinoma is limited. We investigated the efficacy and safety of apatinib for relapsed and refractory nasopharyngeal carcinoma in an open-label, single-arm, phase II clinical trial. Fifty-one patients with relapsed and refractory nasopharyngeal carcinoma in the First Affiliated Hospital, Zhengzhou University, who met the inclusion criteria were enrolled in the study. All patients received apatinib at an initial dose of 500 mg daily (1 cycle = 28 days). The primary and secondary endpoints were overall response rate, progression-free survival, and overall survival. We evaluated treatment effects and recorded apatinib-related adverse events by performing regular follow-ups and workup. The overall response rate (complete and partial responses) was 31.37% (16/51). The median overall survival and progression-free survival were 16 (95% CI, 9.32-22.68) and 9 months (95% CI, 5.24-12.76), respectively. Most patients tolerated treatment-related adverse events of grades 1 and 2; hypertension (29, 56.86%), proteinuria (25, 49.02%), and hand-foot syndrome (27, 52.94%) were the most common adverse events. There were no treatment-related deaths. Apatinib showed good efficacy and safety in patients with relapsed and refractory NPC.
A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11). [2022]Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy.
Expression of Immune Checkpoint Regulators, Cytotoxic T-Lymphocyte Antigen-4, and Programmed Death-Ligand 1 in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma. [2022]Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function.
Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma. [2022]Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients.