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

Non-small Cell Lung Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03064854
• Other study ID #: CPDR001C2101
• Secondary ID: 2016-002815-17
• Status: Terminated
• Phase: Phase 1
• Start date: May 24, 2017
• Est. completion date: July 28, 2021

Study information

• Verified date: August 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 111
• Est. completion date: July 28, 2021
• Est. primary completion date: July 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• PDR001
Powder for solution for infusion
• Cisplatin
Intravenous infusion
• Gemcitabine
Intravenous infusion
• Pemetrexed
Intravenous infusion
• Carboplatin
Intravenous infusion
• Paclitaxel
Intravenous infusion
• Canakinumab
Subcutaneous injection

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Roeselare
Canada	Novartis Investigative Site	Toronto	Ontario
Czechia	Novartis Investigative Site	Praha 4
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Marseille Cedex 05
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Koeln
Hong Kong	Novartis Investigative Site	Pokfulam
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Meldola	FC
Italy	Novartis Investigative Site	Rozzano	MI
Korea, Republic of	Novartis Investigative Site	Seoul
Netherlands	Novartis Investigative Site	Amsterdam
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
United States	Henry Ford Health System SC	Detroit	Michigan
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Washington University School of Medicine SC	Saint Louis	Missouri
United States	UCLA Santa Monica Hematology / Oncology SC-2	Santa Monica	California
United States	Stanford Cancer Center SC	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy	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	42 days
Primary	Overall response rate (ORR) per local investigator assessment for groups A, B and C	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	From baseline up to approximately 28 months
Secondary	Overall Response Rate (ORR) per local investigator assessment for group E	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	Up to approximately 28 months
Secondary	Progression Free Survival (PFS) per Investigator	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	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
Secondary	Disease Control Rate (DCR) per Investigator	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.	Up to approximately 28 months
Secondary	Duration of Response (DOR) per Investigator	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	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
Secondary	Time to Response (TTR) per Investigator	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	From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months
Secondary	Overall survival (OS)	OS is defined as the time from date of start of treatment to date of death due to any cause.	from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years)
Secondary	Trough plasma Concentration (Ctrough) of PDR001	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	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
Secondary	Trough plasma Concentration (Ctrough) of chemotherapy	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	Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
Secondary	Trough plasma Concentration (Ctrough) of canakinumab	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
Secondary	PDR001 Antidrug antibodies (ADA) prevalence at baseline	Blood samples will be collected at indicated time points for immunogenicity analysis.	Baseline
Secondary	Canakinumab ADA prevalence at baseline	Blood samples will be collected at indicated time points for immunogenicity analysis.	Baseline
Secondary	PDR001 ADA incidence during treatment	Blood samples will be collected at indicated time points for immunogenicity analysis.	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
Secondary	Canakinumab ADA incidence during treatment	Blood samples will be collected at indicated time points for immunogenicity analysis.	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
Secondary	Incidence of Adverse Events (AEs)	Incidence of AEs (CTCAE v4.03)	through study completion, up to approximately 3.5 years

External Links

•   A Plain Language Trial Summary is available on novctrd.com
•   Results for CPDR001C2101 from the Novartis Clinical Trial Website