Relatlimab + Immunotherapy for Nasopharyngeal Cancer

Recruiting at 74 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune diseases, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 37

156 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have any active infections requiring IV treatments or be on immunosuppressive medications within 14 days of registration. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug Relatlimab + Immunotherapy for Nasopharyngeal Cancer?

Research shows that nasopharyngeal cancer is sensitive to immunotherapy, especially drugs that target immune checkpoints like PD-1 inhibitors. Similar treatments, such as tislelizumab combined with chemotherapy, have shown to significantly improve progression-free survival in patients with recurrent or metastatic nasopharyngeal cancer. ^{1 2 3 4 5}

Is the combination of Relatlimab and Nivolumab safe for treating nasopharyngeal cancer?

Nivolumab, a drug similar to Relatlimab, has been shown to have a manageable safety profile in treating nasopharyngeal cancer, with common side effects including mild to moderate reactions. Serious side effects are less common, but they can occur, so it's important to discuss potential risks with your doctor. ^{6 7 8 9 10}

How is the drug Relatlimab + Nivolumab unique for nasopharyngeal cancer?

Relatlimab combined with Nivolumab is unique because it involves a novel combination of immune checkpoint inhibitors, which target different pathways to enhance the immune system's ability to fight nasopharyngeal cancer. This approach is distinct from traditional chemotherapy and other single-agent immunotherapies, offering a potentially more effective treatment option for patients with this challenging condition. ^{2 11 12 13 14}

What is the purpose of this trial?

This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The usual approach of treatment is initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is finished, patients may continue to receive additional immunotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend the time without the tumor cells growing or spreading longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.

Research Team

Brigette B Ma

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with recurrent or metastatic nasopharyngeal cancer, positive for Epstein-Barr virus. They must have measurable disease and be stable if they've had brain metastases treated. Good performance status (able to carry out daily activities) is required, and women of childbearing potential need a negative pregnancy test.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

My tumor is positive for Epstein-Barr virus, or I have had detectable EBV DNA in my blood.

I have stable brain metastases for 2+ months and stopped steroids over 4 weeks ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Therapy

Patients receive nivolumab, cisplatin or carboplatin, and gemcitabine. Treatment repeats every 21 days for up to 6 cycles.

18 weeks

6 visits (in-person)

Maintenance Therapy

Patients receive nivolumab with or without relatlimab. Cycles repeat every 4 weeks for up to 2 years.

104 weeks

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 6 years

Every 4 months for 2 years, every 6 months in years 3-5, then annually

Treatment Details

Interventions

• Nivolumab
• Relatlimab

Trial Overview The trial tests adding Relatlimab to standard immunotherapy after initial chemotherapy for nasopharyngeal cancer. It compares the usual treatment (chemo with Cisplatin or Carboplatin plus Gemcitabine, followed by Nivolumab) against this regimen plus Relatlimab to see if it better controls tumor growth.

Participant Groups

Group I: Induction therapy (Platinum-gemcitabine-nivolumab) Experimental Treatment 7 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle, cisplatin IV or carboplatin IV over 30-60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection during screening and on study.

Group II: Arm II (Nivolumab, relatlimab) Experimental Treatment 7 Interventions

Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.

Group III: Arm I (Nivolumab) Active Control 6 Interventions

Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nasopharyngeal carcinoma (NPC) is closely linked to Epstein-Barr virus infection and shows a strong response to radiation and chemotherapy, making it a significant target for immunotherapy, particularly immune checkpoint inhibitors.

A recent clinical trial planning meeting, sponsored by the National Cancer Institute, aimed to develop phase II and III trials for NPC, focusing on various stages of the disease, which could also inform treatment strategies for other cancers driven by viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy. Le, QT., Colevas, AD., O'Sullivan, B., et al.[2021]

In a study of 263 treatment-naive patients with recurrent/metastatic nasopharyngeal cancer, the combination of tislelizumab (a checkpoint inhibitor) and chemotherapy significantly improved progression-free survival compared to placebo plus chemotherapy, with a hazard ratio of 0.52, indicating a strong benefit.

The safety profile of tislelizumab-chemotherapy was comparable to that of the placebo-chemotherapy group, and gene expression profiling suggested that certain tumor characteristics, like an activated dendritic cell signature, may help identify patients who would benefit most from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). Yang, Y., Pan, J., Wang, H., et al.[2023]

In a study of 64 patients with recurrent/metastatic nasopharyngeal carcinoma undergoing anti-PD-1 therapy, baseline levels of lactate dehydrogenase (LDH) were found to be a strong independent predictor of overall survival, with higher LDH levels correlating with shorter survival times.

The number of pretreatment metastases was also a significant predictor of both progression-free survival and overall survival, indicating that patients with fewer metastases may have better outcomes with anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretreatment Serum Lactate Dehydrogenase and Metastases Numbers as Potential Determinants of Anti-PD-1 Therapy Outcome in Nasopharyngeal Carcinoma. Ali, WAS., Huang, X., Wu, Y., et al.[2023]

A prognostic model developed from a study of 524 metastatic nasopharyngeal carcinoma patients can effectively stratify individuals into low-risk and high-risk groups, predicting progression-free survival (PFS) with good accuracy (c-index of 0.71).

In high-risk patients, the combination of chemotherapy and PD-1 inhibitor significantly improved PFS compared to chemotherapy alone (10.6 vs. 9.3 months), while no significant benefit was observed in low-risk patients, suggesting targeted therapy may be more effective for those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a prognostic model to identify the metastatic nasopharyngeal carcinoma patients who may benefit from chemotherapy combination PD-1 inhibitor. Liu, GY., Lu, N., Bei, WX., et al.[2023]

In a study of 86 patients with non-metastatic nasopharyngeal carcinoma, high levels of PD-L1 expression were found to be associated with poorer disease-free survival, indicating that PD-L1 may serve as a prognostic marker for this cancer.

Additionally, a low tumor regression rate after chemoradiotherapy was linked to unfavorable outcomes, suggesting that both PD-L1 expression and tumor response to treatment are important factors in predicting patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of PD-L1 and tumor regression rate on prognosis of nasopharyngeal carcinoma. Zhang, N., Hu, C.[2022]

In a comparison of anti-PD-1 drugs for recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), camrelizumab showed the highest objective response rate (34.1%) among second-line therapies, while first-line nivolumab achieved a 40% response rate, indicating its effectiveness in treating this cancer.

Nivolumab and pembrolizumab demonstrated the best safety profiles for managing adverse events, particularly for lower-grade side effects, while camrelizumab combined with chemotherapy resulted in a significantly higher response rate (90.9%) compared to chemotherapy alone (64.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lv, JW., Li, JY., Luo, LN., et al.[2020]

In a study of 206 patients with locoregionally advanced nasopharyngeal carcinoma, the combination of induction chemotherapy (IC) with the anti-PD-1 inhibitor showed a significantly higher overall response rate (ORR) of 94.7% for primary nasopharynx foci compared to 68.6% for IC alone and 67.9% for IC with anti-EGFR.

The addition of anti-PD-1 not only improved short-term efficacy but also demonstrated tolerable toxicity levels, with no significant differences in common adverse effects among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term efficacy and safety of induction chemotherapy combined with PD-1 inhibitor or anti-EGFR in locoregionally advanced nasopharyngeal carcinoma. Xiang, X., Chen, P., Lan, F., et al.[2023]

In a study of 49 patients with low-risk T4 stage nasopharyngeal carcinoma, the combination of concurrent chemoradiotherapy and Nimotuzumab achieved a remarkable overall survival rate of 89.7% over three years, indicating high efficacy in treatment.

The treatment was well-tolerated, with mild toxicities; the most common acute side effect was mucositis, and late effects included mild xerostomia in some patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of concurrent chemoradiotherapy combined with nimotuzumab for low-risk T4 stage nasopharyngeal carcinoma: A pilot study. Zhang, S., Huang, X., Zhou, L., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a study of 126 patients with locally advanced nasopharyngeal carcinoma, the combination of nimotuzumab with cisplatin and 5-fluorouracil (NPF group) showed significantly better clinical outcomes compared to the docetaxel, cisplatin, and fluorouracil regimen (TPF group), with higher objective response rates (78.5% vs. 58.5%) and disease control rates (93.8% vs. 80.0%).

Patients in the NPF group experienced fewer adverse effects, particularly less leukopenia, and reported improved quality of life scores, along with a longer median overall survival of 18.9 months compared to 16.3 months in the TPF group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of nimotuzumab and PF induction chemotherapy combined with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal carcinoma. Gao, M., Yuan, T., Zhang, F.[2021]

In a phase 2 trial involving 33 patients with metastatic nasopharyngeal carcinoma (mNPC) who had previously failed platinum-based chemotherapy, the combination of sintilimab and bevacizumab showed a promising objective response rate (ORR) of 54.5%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with manageable side effects; the most common adverse event was mild hypothyroidism, and no treatment-related deaths were reported, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: an open-label phase 2 study. Lu, N., Jiang, YF., Xia, WX., et al.[2023]

Immune checkpoint inhibitors (ICIs), particularly PD-1 inhibitors, have shown significant promise in treating nasopharyngeal carcinoma (NPC), with approvals for use in refractory and metastatic cases, as well as in combination with chemotherapy.

Current research is exploring various immunotherapy strategies beyond PD-1 inhibitors, including combinations with antiangiogenic agents and cancer vaccines, highlighting the evolving landscape of personalized treatment options for NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and advances of immunotherapy in nasopharyngeal carcinoma. Xu, JY., Wei, XL., Wang, YQ., et al.[2022]

Nasopharyngeal carcinoma (NPC) is a unique type of head and neck cancer that can be influenced by the presence of the Epstein-Barr virus (EBV), and it presents distinct challenges in treatment due to its different subtypes.

Current treatment recommendations for recurrent NPC primarily involve platinum-based combination chemotherapy, but no immune checkpoint inhibitors have been approved for NPC, highlighting the need for further research to identify effective therapies for this complex disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading? Juarez-Vignon Whaley, JJ., Afkhami, M., Onyshchenko, M., et al.[2023]

In a study of 67 patients with recurrent and metastatic nasopharyngeal carcinoma, combining anti-PD1 checkpoint inhibitors with chemotherapy resulted in a significantly higher objective response rate (ORR) of 53.8% compared to 14.6% for anti-PD1 alone.

The combination therapy also led to improved progression-free survival (PFS) and overall survival (OS) at 6 months, with rates of 65.4% and 100.0% respectively, compared to 28.6% and 73.5% for the anti-PD1 only group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma. Jin, T., Zhang, Q., Jin, QF., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Pretreatment Serum Lactate Dehydrogenase and Metastases Numbers as Potential Determinants of Anti-PD-1 Therapy Outcome in Nasopharyngeal Carcinoma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Development of a prognostic model to identify the metastatic nasopharyngeal carcinoma patients who may benefit from chemotherapy combination PD-1 inhibitor. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Effect of PD-L1 and tumor regression rate on prognosis of nasopharyngeal carcinoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The short-term efficacy and safety of induction chemotherapy combined with PD-1 inhibitor or anti-EGFR in locoregionally advanced nasopharyngeal carcinoma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy of concurrent chemoradiotherapy combined with nimotuzumab for low-risk T4 stage nasopharyngeal carcinoma: A pilot study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

10. Cyprus pubmed.ncbi.nlm.nih.gov

Effect of nimotuzumab and PF induction chemotherapy combined with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal carcinoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: an open-label phase 2 study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Current status and advances of immunotherapy in nasopharyngeal carcinoma. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading? [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma. [2021]