Toripalimab + Chemotherapy for Nasopharyngeal Cancer

(TRANSPARENT Trial)

Recruiting at 8 trial locations

Overseen By Clinical Operations Team Clinical Operations

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Coherus Biosciences, Inc.

Must not be taking: Steroids

Disqualifiers: Local therapy, CNS metastases, 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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination of Toripalimab, Cisplatin, and Gemcitabine for treating nasopharyngeal cancer?

Research shows that combining gemcitabine and cisplatin is effective for treating recurrent or metastatic nasopharyngeal cancer, suggesting that this combination can help control the disease. ^{1 2 3 4 5}

Is the combination of Toripalimab, Cisplatin, and Gemcitabine safe for treating nasopharyngeal cancer?

Studies have shown that the combination of Gemcitabine and Cisplatin, which are part of the treatment, has been evaluated for safety in nasopharyngeal cancer. While some patients experienced significant side effects, the treatment was generally considered to have acceptable safety levels. ^{1 5 6 7 8}

What makes the drug Toripalimab combined with chemotherapy unique for nasopharyngeal cancer?

The drug Toripalimab, when combined with standard chemotherapy (Cisplatin and Gemcitabine), offers a unique advantage for treating nasopharyngeal cancer by significantly improving progression-free survival compared to chemotherapy alone, due to its action as a PD-1 inhibitor that helps the immune system attack cancer cells more effectively. ^{4 9 10 11 12}

What is the purpose of this trial?

This study aims to investigate toripalimab with chemotherapy in participants with nasopharyngeal cancer.

Eligibility Criteria

This trial is for people with nasopharyngeal cancer that has come back or spread, regardless of their HPV status. Participants must have had at least a 6-month gap since their last radiotherapy or chemotherapy and show measurable signs of the disease based on specific criteria.

Inclusion Criteria

My cancer is linked to the Epstein-Barr virus.

My cancer can be measured and has grown in previously treated areas.

My cancer is not linked to Epstein-Barr virus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy-based treatment

Participants receive a combination of toripalimab, cisplatin (or carboplatin), and gemcitabine

6-12 weeks

Maintenance treatment

Participants continue with single-agent toripalimab

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Toripalimab

Trial Overview The study tests Toripalimab in combination with chemotherapy drugs Cisplatin and Gemcitabine. Some participants may receive Carboplatin instead. The goal is to see how well these treatments work together against recurrent metastatic nasopharyngeal cancer.

Participant Groups

Group I: Toripalimab + cisplatin (or carboplatin) + gemcitabine Experimental Treatment 4 Interventions

Participants will receive the triple combination of cisplatin, gemcitabine and toripalimab (Chemotherapy-based treatment phase) followed by single-agent toripalimab (Maintenance treatment phase). The use of cisplatin can be substituted with carboplatin from cycle 2 onwards.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Findings from Research

In a study of 100 patients with recurrent/metastatic nasopharyngeal carcinoma, the combination of gemcitabine (GEM) and cisplatin (DDP) showed significantly better therapeutic efficacy compared to the DDP and fluorouracil (FU) combination.

Patients receiving GEM and DDP experienced fewer side effects, a higher 1-year survival rate, and improved quality of life after 6 months, indicating that this treatment is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma. Yang, Q., Nie, YH., Cai, MB., et al.[2022]

In a study of 57 patients with locally advanced nasopharyngeal carcinoma, the short-term efficacy of induction chemotherapy using the TP regimen (docetaxel plus cisplatin) followed by concurrent chemoradiotherapy was found to be similar to that of the DDP regimen (cisplatin) in terms of complete remission rates.

However, the TP regimen resulted in significantly higher rates of severe hematologic toxicity, such as Grade 3-4 leucopenia and neutropenia, necessitating more frequent use of granulocyte colony stimulating factor (G-CSF) for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma]. Xie, FY., Zou, GR., Hu, WH., et al.[2019]

In a study of 22 patients with metastatic nasopharyngeal carcinoma, the TXP chemotherapy regimen resulted in a 72% overall clinical response rate, with 63% achieving partial remission and 9% complete remission.

The TXP regimen demonstrated a median overall survival of 14 months and a 1-year survival rate of 68%, while the main side effects were manageable myelosuppression, indicating that the treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis. Chen, SZ., Chen, XM., Ding, Y., et al.[2018]

In a study of 822 patients with metastatic nasopharyngeal carcinoma (NPC), the gemcitabine + cisplatin (GP) and paclitaxel + cisplatin + 5-fluorouracil (TPF) regimens showed higher response rates compared to the cisplatin + 5-fluorouracil (PF) regimen.

Despite differences in response rates and toxicity among the five chemotherapy regimens, there were no significant differences in progression-free survival or overall survival, indicating that all regimens (PF, TP, GP) are effective first-line treatments for metastatic NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. Jin, Y., Shi, YX., Cai, XY., et al.[2022]

In a Phase II trial involving 52 patients with recurrent or metastatic nasopharyngeal carcinoma, the combination of gemcitabine and cisplatin showed a response rate of 51.9%, indicating it is an effective first-line chemotherapy option.

The treatment was generally well-tolerated, with a median overall survival of 14.6 months, although it did have significant side effects, particularly leucopenia in 61.6% of patients, and one treatment-related death due to severe sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial. Hsieh, JC., Hsu, CL., Ng, SH., et al.[2022]

In a study involving 33 patients with metastatic nasopharyngeal carcinoma, the efficacy of the nolatrexed and cisplatin (LP) regimen was found to be similar to that of the 5-fluorouracil and cisplatin (FP) regimen, with no significant differences in response rates or survival times.

The LP regimen demonstrated lower toxicity, particularly with a significantly reduced incidence of stomatitis compared to the FP regimen, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil. Zheng, J., Lin, J., Wang, L., et al.[2019]

In a phase I/II study involving 47 patients with nasopharyngeal carcinoma, 55% experienced significant acute toxicity (grade 3 or higher) from the weekly carboplatin and radiotherapy regimen, indicating a notable safety concern.

While the toxicity levels were deemed acceptable compared to previous studies, the treatment showed potentially inferior progression-free and overall survival rates, suggesting that carboplatin may not be a suitable replacement for cisplatin in concurrent chemoradiation for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent weekly carboplatin and radiotherapy for nasopharyngeal carcinoma: report of a joint phase II study. Parliament, M., Jha, N., Rapp, E., et al.[2019]

The DXD regimen (cisplatin, capecitabine, and docetaxel) showed promising efficacy in treating refractory or relapsed nasopharyngeal carcinoma, with an overall response rate of 46.4% and a median overall survival of 14 months based on a study of 30 patients.

The treatment was generally well tolerated, with significant toxicities including neutropenia and anemia, but no chemotherapy-related deaths, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcome of docetaxel, capecitabine and cisplatin regimen for patients with refractory and relapsed nasopharyngeal carcinoma who failed previous platinum-based chemotherapy. Gao, Y., Huang, HQ., Bai, B., et al.[2022]

In a phase 3 trial involving 289 patients with recurrent or metastatic nasopharyngeal carcinoma, the addition of toripalimab to standard gemcitabine-cisplatin chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 11.7 months, indicating enhanced treatment efficacy.

While the overall incidence of serious adverse events was similar between the toripalimab and placebo groups, there was a higher occurrence of immune-related adverse events and infusion reactions in the toripalimab group, suggesting a manageable but distinct safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Mai, HQ., Chen, QY., Chen, D., et al.[2022]

In a phase II trial involving 25 patients with recurrent nasopharyngeal carcinoma, toripalimab combined with intensity-modulated radiotherapy (IMRT) resulted in a high overall response rate of 79.2% and disease control in 95.8% of patients at 3 months post-treatment.

The treatment was found to be tolerable, with low incidences of severe acute side effects, although some patients experienced late severe complications such as nasopharyngeal wall necrosis (28.0%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. Hua, Y., You, R., Wang, Z., et al.[2022]

The TPF neoadjuvant chemotherapy regimen (Taxotere, Cisplatin, and 5-Fluorouracil) is safe and effective for treating advanced nasopharyngeal carcinoma, with no dose-limiting toxicities (DLT) observed at lower dose levels.

The recommended maximum tolerated doses for the TPF regimen were established at Taxotere 60 mg/m², Cisplatin 60 mg/m², and 5-Fluorouracil 600 mg/m², with significant toxicities like grade III/IV neutropenia occurring at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of TPF neoadjuvant chemotherapy followed by radical radiotherapy in advanced nasopharyngeal carcinoma. Guo, L., Lin, HX., Xu, M., et al.[2019]

In a phase II study involving 190 patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), the PD-1 inhibitor toripalimab showed an objective response rate (ORR) of 20.5%, with a median duration of response of 12.8 months, indicating its potential efficacy in this challenging patient population.

A significant correlation was found between a ≥ 50% decrease in plasma Epstein-Barr virus (EBV) DNA after 28 days of treatment and a better response to toripalimab, with an ORR of 48.3% in these patients, suggesting that monitoring EBV levels could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). Wang, FH., Wei, XL., Feng, J., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma]. [2019]

3. China pubmed.ncbi.nlm.nih.gov

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

Concurrent weekly carboplatin and radiotherapy for nasopharyngeal carcinoma: report of a joint phase II study. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Treatment outcome of docetaxel, capecitabine and cisplatin regimen for patients with refractory and relapsed nasopharyngeal carcinoma who failed previous platinum-based chemotherapy. [2022]

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

Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. [2022]

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

Phase I study of TPF neoadjuvant chemotherapy followed by radical radiotherapy in advanced nasopharyngeal carcinoma. [2019]

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

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). [2023]