Clinical trial NCT03064854: PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients
Official title: Phase Ib, Multicenter, Open Label Study of PDR001 in Combination With Platinum Doublet Chemotherapy and Other Immunooncology Agents in PD-L1 Unselected, Metastatic NSCLS Patients (ElevatION:NSCLC-101 Trial)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: PDR001
immunotherapy
Non-small cell lung cancer
lung
NSCLC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-02-27
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to establish the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of PDR001 when administered in combination with platinum-doublet chemotherapy and other immunooncology agent(s) in treatment naive patients with PD-L1 unselected, advanced NSCLC, and to estimate the preliminary anti-tumor activity in this patient population.


Eligibility criteria: Main Inclusion Criteria:

1. Patient has stage IIIB (and is not a candidate for definitive multimodality therapy) or has stage IV NSCLC or relapsed locally advanced or metastatic NSCLC as follows:

   1. Group A, group B and group C only: Patients not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, targeted therapy, monoclonal antibody therapy including immunotherapy (e.g. PD-1/PD-L1 inhibitors) or targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy as depicted in inclusion criterion 4.
   2. Group D only: Patients who have received only one prior systemic therapy treatment consisting of a PD-1 and/or PD-L1 inhibitor with or without a CTLA4 inhibitor for NSCLC, with exception of neo-adjuvant or adjuvant therapy as depicted in inclusion criterion 4. The last dose of prior immunotherapy must have been administered at least 6 weeks prior to the start of study treatment (cycle 1 day 1).
2. Histologically or cytologically confirmed diagnosis of NSCLC that is EGFR Wild-type, ALK-negative rearrangement and ROS1-negative rearrangement
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
4. Patients with at least 1 measurable tumor lesion as assessed by Computed Tomography (CT) Scan or Magnetic Resonance Imaging (MRI) according to RECIST 1.1.

Main Exclusion Criteria:

1. Patient with a history of severe hypersensitivity reaction to the planned study treatment including gemcitabine, paclitaxel, cisplatin, carboplatin, pemetrexed or any known excipients of these drugs
2. History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
3. Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
4. History of leptomeningeal metastases
5. Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy
timeFrame: 42 days
measure: Overall response rate (ORR) per local investigator assessment for groups A, B and C
timeFrame: From baseline up to approximately 28 months
Secondary outcomes:
measure: Overall Response Rate (ORR) per local investigator assessment for group E
timeFrame: Up to approximately 28 months
measure: Progression Free Survival (PFS) per Investigator
timeFrame: From start of treatment to the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 28 months
measure: Disease Control Rate (DCR) per Investigator
timeFrame: Up to approximately 28 months
measure: Duration of Response (DOR) per Investigator
timeFrame: From date of first documented response to the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 28 months
measure: Time to Response (TTR) per Investigator
timeFrame: From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months
measure: Overall survival (OS)
timeFrame: from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years)
measure: Trough plasma Concentration (Ctrough) of PDR001
timeFrame: Pre-infusion on Day 1 of Cycle 1 to 4 of induction phase; pre-infusion on Day 1 of Cycle 1 to 4, 6, 8 and every 6 cycle afterwards of maintenance phase; Cycle = 21 Days
measure: Trough plasma Concentration (Ctrough) of chemotherapy
timeFrame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
measure: Trough plasma Concentration (Ctrough) of canakinumab
timeFrame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
measure: PDR001 Antidrug antibodies (ADA) prevalence at baseline
timeFrame: Baseline
measure: Canakinumab ADA prevalence at baseline
timeFrame: Baseline
measure: PDR001 ADA incidence during treatment
timeFrame: Pre-infusion on Day 1 of Cycle 1 to 4 of induction phase, pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 6, 8 and every 6 cycle afterwards of maintenance phase, end of treatment and 30 and 150-day post-treatment
measure: Canakinumab ADA incidence during treatment
timeFrame: Pre-infusion on Day 1 of Cycle 1 and 4 of induction phase, pre-infusion on Day 1 of Cycle 6, 14 and 20 of maintenance phase, end of treatment and 30 and 150-day post-treatment
measure: Incidence of Adverse Events (AEs)
timeFrame: through study completion, up to approximately 3.5 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Santa Monica
country: United States
facility: UCLA Santa Monica Hematology / Oncology SC-2
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center SC
state: California
city: Detroit
country: United States
facility: Henry Ford Health System SC
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine SC
state: Missouri
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Roeselare
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Marseille Cedex 05
country: France
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: