Phase III Study of Camrelizumab in Combination With Chemotherapy in Recurrent/Metastatic Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT03707509
• Recruitment Status: Active, not recruiting
• First Posted: October 16, 2018
• Last Update Posted: July 1, 2022
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: September 25, 2018
• First Posted Date: October 16, 2018
• Last Update Posted Date: July 1, 2022
• Actual Study Start Date: November 13, 2018
• Actual Primary Completion Date: August 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2018)

Progression-free survival (PFS) [ Time Frame: up to 24 month ]

PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee according to RECIST v1.1 or death from any cause, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 14, 2018)

• Progression-free survival [ Time Frame: up to 24 month ]
  Progression-free survival (PFS) assessed by investigators according to RECIST V 1.1
• Objective Response Rate (ORR) [ Time Frame: up to 24 month ]
  The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1
• Disease Control Rate (DCR) Disease Control Rate (DCR) [ Time Frame: up to 24 month ]
  The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1
• Duration of Response (DoR) [ Time Frame: up to 24 month ]
  According to Recist v 1.1 accessed by investigators
• 2 years Overall Survival (OS) rate [ Time Frame: up to 24 month ]
  The percentage of patients overall survival in 2 years
• Adverse Events (AEs) [ Time Frame: up to 24 month ]
  All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 4.03

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 14, 2018)

Antidrug Antibodies (ADAs) [ Time Frame: up to 24 month ]

To evaluate the incidence and titers of ADAs against camrelizumab

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Phase III Study of Camrelizumab in Combination With Chemotherapy in Recurrent/Metastatic Nasopharyngeal Carcinoma
• Official Title: A Phase III, Randomized, Double-Blind, Multi-center Study to Investigate the Efficacy and Safety of Camrelizumab+Gemcitabine+Cisplatin Versus Placebo+Gemcitabine+Cisplatin in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma
• Brief Summary: This study is a randomized, placebo-controlled, double-blind, multicenter phase III clinical study. Target population is patients with recurrent/metastatic nasopharyngeal carcinoma who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of camrelizumab in combination with gemcitabine and cisplatin with placebo in combination with gemcitabine and cisplatin in study population in China. camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.
• Detailed Description: In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Treatment cycles of chemotherapy will be at most 6 weeks which will be decided by investigators. Progression-free survival (PFS) determined by the Independent Review Committee (IRC) will be the primary outcome measures.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Nasopharyngeal Carcinoma

Intervention

• Drug: Camrelizumab
  Maximum 6 cycles for combined therapy. Camrelizumab maintenance.
  Other Name: SHR-1210
• Drug: Placebos
  Maximum 6 cycles for combined therapy.
  Other Name: Placebo - Concentrate
• Drug: Gemcitabine
  Maximum 6 cycles for combined therapy.
  Other Name: Gemcitabine Hydrochloride for Injection
• Drug: Cisplatin
  Maximum 6 cycles for combined therapy.
  Other Name: Cisplantin Injection

Study Arms

• Experimental: Camrelizumab + Gemcitabine + Cisplatin
  subject will receive camrelizumab 200mg every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles
  Interventions:

  • Drug: Camrelizumab
  • Drug: Gemcitabine
  • Drug: Cisplatin
• Active Comparator: Placebos + Gemcitabine + Cisplatin
  subject will receive placebos every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles
  Interventions:

  • Drug: Placebos
  • Drug: Gemcitabine
  • Drug: Cisplatin

• Publications *: Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 30, 2022): 263
• Original Estimated Enrollment (submitted: October 14, 2018): 250
• Estimated Study Completion Date: December 31, 2022
• Actual Primary Completion Date: August 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤75 years;
2. Subjects with histopathological diagnosis of nasopharyngeal carcinoma;
3. Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment;
4. Has not received prior systemic treatment;
5. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
6. Subject must have a measurable target lesion based on RECIST v1.1;

Exclusion Criteria:

1. Allergic to monoclonal antibodies, any camrelizumab components, gemcitabine, cisplatin and other platinum drugs;

2. Prior therapy as follow:

   • Anti-PD-1 or anti-PD-L1;
   • Received last dose of anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within 4 weeks of the first dose of study medication;
   • Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone or equivalent for replacement therapy;
   • Received major operations or serious injuries within 4 weeks of the first dose of study medication;
3. Not recovered to ≤CTCAE 1 from adverse events (except for hair loss) due to a previously anti-tumor treatment;
4. Pregnancy or breast feeding;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03707509
• Other Study ID Numbers: SHR-1210-III-308
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Li Zhang, MD; Cancer Center of Sun-Yat Sen University (CCSYSU)
• Study Director: Qing Yang, MD; Jiangsu HengRui Medicine Co., Ltd.

• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: June 2022