A Phase II Clinical Study of Treprilimab in the Treatment of Recurrent Nasopharyngeal Carcinoma After Re-irradiation

Study Overview
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Brief Summary
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To establish the antitumor activity and safety of the anti-programmed death 1 receptor monoclonal antibody, Treprilimab, in patients with local recurrent/residual nasopharyngeal carcinoma after re-irradiation.Patients with local recurrent/residual NPC after re-irradiation were treated with Treprilimab until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity.The sample size of this study was estimated on the assumption that response rates (RRs) to Treprilimab should be around 25%,based on a report that was available at the time this study was planned.Furthermore, the RR to noncytotoxic, experimental agents such as pazopanib and cetuximab in similarly pretreated patient cohorts was approximately 5% to 10%. This study's design was based on the modiﬁed Simon two-stage optimal design (α=0.05，β=0.2,n1=2/22,n2=7/40). If two responses were observed during the ﬁrst stage, enrollment was continued until a total of 40 patients was reached.

Detailed Description
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To establish the antitumor activity and safety of the anti-programmed death 1 receptor monoclonal antibody, Treprilimab, in patients with local recurrent/residual nasopharyngeal carcinoma after re-irradiation.Patients with local recurrent/residual NPC after re-irradiation were treated with Treprilimab until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity.The sample size of this study was estimated on the assumption that response rates (RRs) to Treprilimab should be around 25%,based on a report that was available at the time this study was planned.Furthermore, the RR to noncytotoxic, experimental agents such as pazopanib and cetuximab in similarly pretreated patient cohorts was approximately 5% to 10%. This study's design was based on the modiﬁed Simon two-stage optimal design (α=0.05，β=0.2,n1=2/22,n2=7/40). If two responses were observed during the ﬁrst stage, enrollment was continued until a total of 40 patients was reached. The target lesions had to be measurable by the Response Evaluation Criteria in Solid Tumors (RECIST). Radiologic assessments were performed every 8 weeks for 6 months and then every 12 weeks thereafter. Eligible patients were treated with Treprilimab at a dosage of 240mg intravenously every 3 weeks until they experienced disease progression or unacceptable toxicity. The primary end point of this study was objective response by the RECIST criteria , and the secondary end points were overall survival (OS), progression-free survival (PFS), duration of response and toxicity.

Official Title
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A Phase II Single Arm Clinical Study of Treprilimab in the Treatment of Local Recurrent/Residual Nasopharyngeal Carcinoma After Re-irradiation

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Treprilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ages from 18 years to 65 years. Histologically confirmed local recurrent/residual Nasopharyngeal carcinoma with previous re-irradiation. measurable disease at baseline on the basis of RECIST v1.1. Eastern Cooperative Oncology Group performance status of 0 or 1. adequate organ function. anticipate survival≥3 months. Exclusion Criteria: a diagnosis of immuno deﬁciency or systemic corticosteroid therapy within 14 days of study start. prior anticancer monoclonal antibody therapy within 4 weeks of study start. any anticancer therapy within 4 weeks preceding the study start. therapy with any other immune checkpoint inhibitor. active autoimmune disease, interstitial lung disease, known additional malignancy that was progressing or that required active treatment. not received platinum based chemotherapy previously. confirmed systemic metastasis HBV positive and Child-Pugh B or C cirrhosis HCV positive and Child-Pugh B or C cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treprilimab treatment group<br>Treprilimab 240mg ivdrip Q3W until progression or unacceptable toxicity | Drug: Treprilimab<br>* Treprilimab 240mg Q3W until progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the proportion of patients with conﬁrmed complete response or partial response (PR) per RECIST v1.1 | Response was assessed by magnetic resonance imaging every 8 weeks for the ﬁrst 6 months and every 12 weeks thereafter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | progression free survival | time from enrollment to the ﬁrst documented progression of disease or death from any cause) | 
| OS | overall survival | time from enrollment to death from any cause | 
| Number of participants with treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | through the study and for 30 days after treatment discontinuation (90 days for serious AEs). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treprilimab,recurrent/residual NPC