Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

NCT02605967 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CPDR001X22012015-000454-38
• Study Type: interventional
• Target: 122
• Locations: 7 countries
• Sites: 18

Brief Summary

The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced nasopharyngeal carcinoma (NPC). By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, PDR001 leads to the activation of a T-cell mediated antitumor immune response.

Conditions

Nasopharyngeal Carcinoma

Keywords

PDR001; nasopharyngeal cancer; moderately differentiated/undifferentiated; locally advanced; recurrent or metastatic NPC; after first- line platinum-based therapy

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death

  PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Number of participants in each category (progression, death, censored) is reported in this record.

  From randomization up to maximum 3.3 years

• Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Median PFS

  PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

  From randomization up to maximum 3.3 years

Secondary Outcomes (18)

• Overall Survival (OS)

  From randomization up to maximum 4.8 years.

• Overall Response Rate (ORR) as Per RECIST v 1.1

  From randomization up to maximum 3.3 years

• Duration of Response (DOR) as Per RECIST v 1.1

  From randomization up to maximum 3.3 years

• Time to Progression (TTP) as Per RECIST v 1.1

  From randomization up to maximum 3.3 years

• Immune-related Progression-free Survival (irPFS) as Per irRC

  From randomization up to maximum 3.3 years

Study Arms (2)

Spartalizumab 400 mg Q4W

EXPERIMENTAL

anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab

Drug: Spartalizumab

Chemotherapy

ACTIVE COMPARATOR

commonly used chemotherapy as per investigator's choice

Drug: Investigator choice of chemotherapy

Interventions

Spartalizumab DRUG

Spartalizumab was administered via intravenous infusion at a dose of 400 mg every 4 weeks (Q4W). Spartalizumab is a humanized anti-PD-1 IgG4 antibody which blocks the binding of PD1 to its ligands PD-L1 and PD-L2.

Also known as: PDR001

Spartalizumab 400 mg Q4W

Investigator choice of chemotherapy DRUG

Commonly used chemotherapy as per investigator's choice. The dose and route of administration was the one described in each drug's label.

Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
• Must be resistant to platinum-based chemotherapy (defined as progression on or after platinum-based chemotherapy given in the recurrent/metastatic setting).
• May have received at least 1 prior therapy for recurrent or metastatic disease, up to 2 prior systemic therapies.
• An archival tumor specimen or newly obtained tumor sample may be submitted at screening/baseline (a fresh tumor sample is preferred), unless agreed differently between Novartis and the Investigator.
• At least 1 measurable lesion (as per RECIST v1.1) progressing or new since last anti-tumor therapy.
• Prior treated brain or meningeal metastases must be without MRI evidence of progression for at least 8 weeks and off systemic steroids for at least 2 weeks prior to screening/baseline.
• Patient must be willing to undergo testing for human immunodeficiency virus (HIV) if not tested within the past 6 months. If HIV+ positive, patient will be eligible if: his/ her CD4+ count ≥ 300/μL; his/her viral load is undetectable; he/she is currently receiving highly active antiretroviral therapy (HAART).

You may not qualify if:

• History of severe hypersensitivity reactions to other mAbs
• Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators.
• Active HBV or HCV infections requiring therapy.
• Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.
• Patients receiving systemic treatment with any immunosuppressive medication.
• Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Northwest Georgia Oncology Center NWGA Onc - Carrollton

Marietta, Georgia, 30060, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

NYU Laura and Isaac Perlmutter Cancer Center Laura & Isaac Perlmutter Ctr

New York, New York, 10016, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Nice, Alpes Maritimes, 06189, France

Location

Novartis Investigative Site

Villejuif, Villejuif, 94800, France

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Kowloon, Hong Kong

Location

Novartis Investigative Site

Tuenmen, Hong Kong

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Tainan, Taiwan ROC, 70403, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Taoyuan District, 33305, Taiwan

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Even C, Wang HM, Li SH, Ngan RK, Dechaphunkul A, Zhang L, Yen CJ, Chan PC, Chakrabandhu S, Ma BBY, Tanasanvimon S, Lee VHF, Lou PJ, Li Z, Spira AI, Sukari A, Guigay J, McCune S, Gonzalez-Maffe J, Szpakowski S, Yao Y, Liang H, Mataraza J, Sechaud R, Manenti L, Lim DW. Phase II, Randomized Study of Spartalizumab (PDR001), an Anti-PD-1 Antibody, versus Chemotherapy in Patients with Recurrent/Metastatic Nasopharyngeal Cancer. Clin Cancer Res. 2021 Dec 1;27(23):6413-6423. doi: 10.1158/1078-0432.CCR-21-0822. Epub 2021 Aug 25.

  PMID: 34433653 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Disorders of Sex Development; Recurrence

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: November 17, 2015
• Study Start: April 20, 2016
• Primary Completion: November 5, 2019
• Study Completion: February 19, 2021
• Last Updated: February 10, 2022
• Results First Posted: August 12, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share

Locations

TW (4); TH (3); US (4); CN (1); FR (2); HK (3); SG (1)