Principal Investigator Interview: RTOG 3521 Study of Combination Toripalimab and Chemotherapy in Recurrent Metastatic Nasopharyngeal Cancer

April 01, 2024

The RTOG 3521 is a trial that is currently enrolling sites for patients with recurrent, metastatic nasopharyngeal carcinoma that are systemic treatment naïve. This is a single-arm, multicenter, phase IV study of the immunotherapy drug toripalimab in combination with cisplatin and gemcitabine in this patient population. The primary objective of this trial is to determine the efficacy of toripalimab with chemotherapy in terms of objective response rate. A key secondary objective of this study is evaluating the efficacy of toripalimab with chemotherapy in terms of duration of response.

Interview with Anna Spreafico, MD, PhD, of the Princess Margaret Cancer Centre and Principal Investigator of RTOG 3521

Q: Can you provide an overview of the study in your own words?

A: This study is evaluating the role of the combination of chemo-immunotherapy in North America. In particular, RTOG3521 is designed to test the efficacy of the antiPD1 toripalimab in combination with cisplatin and gemcitabine in patients affected by advanced nasopharyngeal cancer. A total of 100 patients with either EBV-positive or negative and HPV-positive or negative, or so-called double negative, nasopharyngeal cancer, who are systemic therapy naïve in the recurrent/metastatic setting will be included in the study.

Q: What is the significance of this study? Does this study have the potential to change practice?

A: This study is important as the efficacy of the combination of antiPD1 with chemotherapy has not yet been confirmed in the North American setting. The results of this study will inform the first-line regimen in the North America population of recurrent/metastatic nasopharyngeal cancer. This study is not randomized but as a single-arm study it is unique in that it offers North American patients the opportunity to be treated with toripalimab, the drug that was proven in the randomized phase III JUPITER-02 trial to improve progression-free and overall survival in these patients when combined with cisplatin and gemcitabine chemotherapy. This study is an opportunity to offer the chemo-immunotherapy combination supported by the highest level evidence at present, to the North American nasopharyngeal cancer population.

Q: What are the most common questions you expect to receive about this study and how would you address them?


  • Will EBV-driven and non-driver nasopharyngeal carcinoma patients be eligible? Yes
  • Will HPV-positive and negative nasopharyngeal carcinoma patients be eligible? Yes
  • Will EBV-negative and HPV-negative nasopharyngeal carcinoma patients be eligible? Yes
  • Will patients pre-exposed to anti PD1 be eligible? No
  • Will EBV and HPV testing be done locally? Yes and both are required to be known at screening.
  • How many cycles of cisplatin-gemcitabine are given? Up to 6 cycles of chemotherapy will be delivered depending on tolerability and response.
  • How many cycles of toripalimab are given? The combination of toripalimab, cisplatin and gemcitabine will be delivered IV on a 3-week schedule for up to 6 cycles. In the post-chemotherapy treatment phase, participants who do not experience progression of disease, will receive maintenance toripalimab, once every 3 weeks, for up to 24 months.
  • How often will patients be assessed for their response to the chemoimmunotherapy? Imaging will be performed every 6 weeks for 12 months following Cycle 1, Day 1 and then every 9 weeks thereafter through safety follow-up visit, regardless of treatment delays, until disease progression per RECIST v1.1, loss of clinical benefit, withdrawal of consent, initiation of new anti-cancer therapy, death, or study termination by the Sponsor.


Q: Is there anything else researchers should know about this study?

A: As this is a rare patient population, the RTOG3521 budget for sites provides excellent startup and accrual support to cover administrative costs even in low accrual scenarios. Also, new guidelines at the NRG Oncology group level allow for between 1-7 RTOG Foundation accruals to be counted as NRG Oncology accrual credits depending on your membership level. We hope that all sites in North America will consider this study as it will be the only contemporary study that was designed and aimed at studying nasopharyngeal carcinoma in North America.


Participate in RTOG Research

To participate as an RTOG study investigator, your organization must be part of the RTOG Foundation network. Patients who wish to participate in a study must be under the care of an RTOG participating investigator. For additional information, email or call 1-215-574-3173.

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