Description:
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.
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CPDR001C2101
- SECONDARY ID:
2016-002815-17
- NCT ID:
NCT03064854
Conditions
- Non-small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
PDR001 | | Group A: squamous, gem/cis+PDR001 |
Cisplatin | | Group A: squamous, gem/cis+PDR001 |
Gemcitabine | | Group A: squamous, gem/cis+PDR001 |
Pemetrexed | | Group B: non-squamous, pem/cis+PDR001 |
Carboplatin | | Group C: paclitaxel/carbo+PDR001 |
Paclitaxel | | Group C: paclitaxel/carbo+PDR001 |
Canakinumab | | Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Group A: squamous, gem/cis+PDR001 | Experimental | | - PDR001
- Cisplatin
- Gemcitabine
|
Group B: non-squamous, pem/cis+PDR001 | Experimental | | - PDR001
- Cisplatin
- Pemetrexed
|
Group C: paclitaxel/carbo+PDR001 | Experimental | | - PDR001
- Carboplatin
- Paclitaxel
|
Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab | Experimental | | - PDR001
- Cisplatin
- Pemetrexed
- Carboplatin
- Canakinumab
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy |
Time Frame: | 42 days |
Safety Issue: | |
Description: | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) per local investigator assessment for group E |
Time Frame: | Up to approximately 28 months |
Safety Issue: | |
Description: | ORR is defined as the proportion of patients with BOR of CR or PR, as per RECIST 1.1 and local investigator assessment for group E |
Measure: | Progression Free Survival (PFS) per Investigator |
Time Frame: | 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 |
Safety Issue: | |
Description: | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, as per RECIST 1.1 and local investigator assessment |
Measure: | Disease Control Rate (DCR) per Investigator |
Time Frame: | Up to approximately 28 months |
Safety Issue: | |
Description: | DCR is the proportion of patients with a BOR of CR or PR or stable disease (SD), as per RECIST 1.1 and local investigator assessment. |
Measure: | Duration of Response (DOR) per Investigator |
Time Frame: | 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 |
Safety Issue: | |
Description: | DOR is defined by responders as the time between the date of first documented response (CR or PR) and the date of first documented progression (RECIST 1.1 and local investigator assessment) or death due any cause |
Measure: | Time to Response (TTR) per Investigator |
Time Frame: | From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months |
Safety Issue: | |
Description: | TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR as per RECIST 1.1 and local investigator assessment |
Measure: | Overall survival (OS) |
Time Frame: | from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years) |
Safety Issue: | |
Description: | OS is defined as the time from date of start of treatment to date of death due to any cause. |
Measure: | Trough plasma Concentration (Ctrough) of PDR001 |
Time Frame: | 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 |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for pharmacokinetic analysis. |
Measure: | Trough plasma Concentration (Ctrough) of chemotherapy |
Time Frame: | Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for pharmacokinetic analysis. Ctrough will be assessed for all chemotherapy agents: cysplatin, pemetrexed, carboplatin and gemcitabine |
Measure: | Trough plasma Concentration (Ctrough) of canakinumab |
Time Frame: | Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for pharmacokinetic analysis. |
Measure: | PDR001 Antidrug antibodies (ADA) prevalence at baseline |
Time Frame: | Baseline |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for immunogenicity analysis. |
Measure: | Canakinumab ADA prevalence at baseline |
Time Frame: | Baseline |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for immunogenicity analysis. |
Measure: | PDR001 ADA incidence during treatment |
Time Frame: | 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 |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for immunogenicity analysis. |
Measure: | Canakinumab ADA incidence during treatment |
Time Frame: | 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 |
Safety Issue: | |
Description: | Blood samples will be collected at indicated time points for immunogenicity analysis. |
Measure: | Incidence of Adverse Events (AEs) |
Time Frame: | through study completion, up to approximately 3.5 years |
Safety Issue: | |
Description: | Incidence of AEs (CTCAE v4.03) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- PDR001
- immunotherapy
- Non-small cell lung cancer
- lung
- NSCLC
Last Updated
August 10, 2021