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

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)

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
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.

Overall Status Active, not recruiting
Start Date 2017-05-24
Completion Date 2021-08-16
Primary Completion Date 2021-08-16
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy 42 days
Overall response rate (ORR) per local investigator assessment for groups A, B and C From baseline up to approximately 28 months
Secondary Outcome
Measure Time Frame
Overall Response Rate (ORR) per local investigator assessment for group E Up to approximately 28 months
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
Disease Control Rate (DCR) per Investigator Up to approximately 28 months
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
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
Overall survival (OS) from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years)
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
Trough plasma Concentration (Ctrough) of chemotherapy Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
Trough plasma Concentration (Ctrough) of canakinumab Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
PDR001 Antidrug antibodies (ADA) prevalence at baseline Baseline
Canakinumab ADA prevalence at baseline Baseline
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
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
Incidence of Adverse Events (AEs) through study completion, up to approximately 3.5 years
Enrollment 112
Condition
Intervention

Intervention Type: Drug

Intervention Name: PDR001

Description: Powder for solution for infusion

Intervention Type: Drug

Intervention Name: Cisplatin

Description: Intravenous infusion

Intervention Type: Drug

Intervention Name: Gemcitabine

Description: Intravenous infusion

Arm Group Label: Group A: squamous, gem/cis+PDR001

Intervention Type: Drug

Intervention Name: Pemetrexed

Description: Intravenous infusion

Intervention Type: Drug

Intervention Name: Carboplatin

Description: Intravenous infusion

Intervention Type: Drug

Intervention Name: Paclitaxel

Description: Intravenous infusion

Arm Group Label: Group C: paclitaxel/carbo+PDR001

Intervention Type: Drug

Intervention Name: Canakinumab

Description: Subcutaneous injection

Arm Group Label: Group E: non-squamous, pem/cis (or carbo)+PDR001+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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Location
Facility:
Highlands Oncology Group | Fayetteville, Arkansas, 72703, United States
UCLA Santa Monica Hematology / Oncology SC-2 | Santa Monica, California, 90404, United States
Stanford Cancer Center SC | Stanford, California, 94305, United States
Henry Ford Health System SC | Detroit, Michigan, 48202, United States
Washington University School of Medicine SC | Saint Louis, Missouri, 63110, United States
Novartis Investigative Site | Leuven, 3000, Belgium
Novartis Investigative Site | Roeselare, 8800, Belgium
Novartis Investigative Site | Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site | Praha 4, 140 59, Czechia
Novartis Investigative Site | Lyon Cedex, 69373, France
Novartis Investigative Site | Marseille cedex 05, 13385, France
Novartis Investigative Site | Gottingen, 37075, Germany
Novartis Investigative Site | Koeln, 51109, Germany
Novartis Investigative Site | Pokfulam, Hong Kong
Novartis Investigative Site | Meldola, FC, 47014, Italy
Novartis Investigative Site | Rozzano, MI, 20089, Italy
Novartis Investigative Site | Aviano, PN, 33081, Italy
Novartis Investigative Site | Seoul, 03080, Korea, Republic of
Novartis Investigative Site | Amsterdam, 1066 CX, Netherlands
Novartis Investigative Site | Singapore, 169610, Singapore
Novartis Investigative Site | Barcelona, Catalunya, 08035, Spain
Novartis Investigative Site | Madrid, 28034, Spain
Novartis Investigative Site | Madrid, 28041, Spain
Location Countries

Belgium

Canada

Czechia

France

Germany

Hong Kong

Italy

Korea, Republic of

Netherlands

Singapore

Spain

United States

Verification Date

2021-05-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Group A: squamous, gem/cis+PDR001

Type: Experimental

Label: Group B: non-squamous, pem/cis+PDR001

Type: Experimental

Label: Group C: paclitaxel/carbo+PDR001

Type: Experimental

Label: Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab

Type: Experimental

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News