PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT03064854

Collaborator

(none)

111

Enrollment

Locations

Arms

50.1

Actual Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: PDR001 Drug: Cisplatin Drug: Gemcitabine Drug: Pemetrexed Drug: Carboplatin Drug: Paclitaxel Drug: Canakinumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

111 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 24, 2017

Actual Primary Completion Date :

Jul 28, 2021

Actual Study Completion Date :

Jul 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: squamous, gem/cis+PDR001	Drug: PDR001 Powder for solution for infusion Drug: Cisplatin Intravenous infusion Drug: Gemcitabine Intravenous infusion
Experimental: Group B: non-squamous, pem/cis+PDR001	Drug: PDR001 Powder for solution for infusion Drug: Cisplatin Intravenous infusion Drug: Pemetrexed Intravenous infusion
Experimental: Group C: paclitaxel/carbo+PDR001	Drug: PDR001 Powder for solution for infusion Drug: Carboplatin Intravenous infusion Drug: Paclitaxel Intravenous infusion
Experimental: Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab	Drug: PDR001 Powder for solution for infusion Drug: Cisplatin Intravenous infusion Drug: Pemetrexed Intravenous infusion Drug: Carboplatin Intravenous infusion Drug: Canakinumab Subcutaneous injection

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy [42 days]
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
Overall response rate (ORR) per local investigator assessment for groups A, B and C [From baseline up to approximately 28 months]
ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 and local investigator assessment for groups A, B and C

Secondary Outcome Measures

Overall Response Rate (ORR) per local investigator assessment for group E [Up to approximately 28 months]
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
Progression Free Survival (PFS) per Investigator [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]
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
Disease Control Rate (DCR) per Investigator [Up to approximately 28 months]
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.
Duration of Response (DOR) per Investigator [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]
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
Time to Response (TTR) per Investigator [From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months]
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
Overall survival (OS) [from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years)]
OS is defined as the time from date of start of treatment to date of death due to any cause.
Trough plasma Concentration (Ctrough) of PDR001 [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]
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Trough plasma Concentration (Ctrough) of chemotherapy [Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days]
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
Trough plasma Concentration (Ctrough) of canakinumab [Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days]
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
PDR001 Antidrug antibodies (ADA) prevalence at baseline [Baseline]
Blood samples will be collected at indicated time points for immunogenicity analysis.
Canakinumab ADA prevalence at baseline [Baseline]
Blood samples will be collected at indicated time points for immunogenicity analysis.
PDR001 ADA incidence during treatment [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]
Blood samples will be collected at indicated time points for immunogenicity analysis.
Canakinumab ADA incidence during treatment [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]
Blood samples will be collected at indicated time points for immunogenicity analysis.
Incidence of Adverse Events (AEs) [through study completion, up to approximately 3.5 years]
Incidence of AEs (CTCAE v4.03)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Main Inclusion Criteria:

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:
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.
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).
Histologically or cytologically confirmed diagnosis of NSCLC that is EGFR Wild-type, ALK-negative rearrangement and ROS1-negative rearrangement
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
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:

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
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.
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).
History of leptomeningeal metastases
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).
Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	UCLA Santa Monica Hematology / Oncology SC-2	Santa Monica	California	United States	90404
3	Stanford Cancer Center SC	Stanford	California	United States	94305
4	Henry Ford Health System SC	Detroit	Michigan	United States	48202
5	Washington University School of Medicine SC	Saint Louis	Missouri	United States	63110
6	Novartis Investigative Site	Leuven		Belgium	3000
7	Novartis Investigative Site	Roeselare		Belgium	8800
8	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
9	Novartis Investigative Site	Praha 4		Czechia	140 59
10	Novartis Investigative Site	Lyon Cedex		France	69373
11	Novartis Investigative Site	Marseille Cedex 05		France	13885
12	Novartis Investigative Site	Gottingen		Germany	37075
13	Novartis Investigative Site	Koeln		Germany	51109
14	Novartis Investigative Site	Pokfulam		Hong Kong
15	Novartis Investigative Site	Meldola	FC	Italy	47014
16	Novartis Investigative Site	Rozzano	MI	Italy	20089
17	Novartis Investigative Site	Aviano	PN	Italy	33081
18	Novartis Investigative Site	Seoul		Korea, Republic of	03080
19	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
20	Novartis Investigative Site	Singapore		Singapore	169610
21	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
22	Novartis Investigative Site	Madrid		Spain	28034
23	Novartis Investigative Site	Madrid		Spain	28041