Clinical trial NCT02605967: Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma
Official title: A Phase II, Open-label, Randomized Controlled Study of PDR001 in Patients With Moderately Differentiated/Undifferentiated Locally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma Who Progressed on Standard Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: PDR001
nasopharyngeal cancer
moderately differentiated/undifferentiated
locally advanced
recurrent or metastatic NPC
after first- line platinum-based therapy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-11-17
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This was an open-label, multi-center, randomized, and controlled Phase II study to evaluate the efficacy and safety of spartalizumab versus investigator's choice of treatment in subjects with moderately differentiated/undifferentiated locally advanced recurrent or metastatic NPC who progressed on or after first-line treatment.

Participants who met the inclusion/exclusion criteria were randomized in a 2:1 ratio to either investigational arm (spartalizumab) or control arm (commonly used chemotherapy as per investigator's choice). Participants treated with spartalizumab could continue treatment until confirmed progressive disease as per immune-related response criteria (irRC). Participants in the chemotherapy arm were allowed to crossover to spartalizumab if they had radiological progression as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) documented by an independent central review and the Investigator believed this was the best treatment option for the patient.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death
timeFrame: From randomization up to maximum 3.3 years
measure: Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Median PFS
timeFrame: From randomization up to maximum 3.3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization up to maximum 4.8 years.
measure: Overall Response Rate (ORR) as Per RECIST v 1.1
timeFrame: From randomization up to maximum 3.3 years
measure: Duration of Response (DOR) as Per RECIST v 1.1
timeFrame: From randomization up to maximum 3.3 years
measure: Time to Progression (TTP) as Per RECIST v 1.1
timeFrame: From randomization up to maximum 3.3 years
measure: Immune-related Progression-free Survival (irPFS) as Per irRC
timeFrame: From randomization up to maximum 3.3 years
measure: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Accumulation Ratio (Racc) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Terminal Elimination Half-life (T1/2) of Spartalizumab
timeFrame: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
measure: Number of Participants With Anti-spartalizumab Antibodies
timeFrame: Baseline (pre-dose on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 655 days).
measure: PD-L1 Percent Positive Tumor
timeFrame: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Percent Marker Area for CD8 Expression in Tumor Samples
timeFrame: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: TIL Count in Tumor Samples
timeFrame: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
measure: Fold Change From Baseline in IFN-gamma Levels in Plasma
timeFrame: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
measure: Fold Change From Baseline in IL-6 Levels in Plasma
timeFrame: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
measure: Fold Change From Baseline in TNF-alfa Levels in Plasma
timeFrame: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
Other outcomes:
Locations:
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center NWGA Onc - Carrollton
state: Georgia
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: NYU Laura and Isaac Perlmutter Cancer Center Laura & Isaac Perlmutter Ctr
state: New York
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
state: Alpes Maritimes
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
state: Villejuif
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Kowloon
country: Hong Kong
facility: Novartis Investigative Site
city: Tuen Mun
country: Hong Kong
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.