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

NCT03064854 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CPDR001C21012016-002815-17
• Study Type: interventional
• Target: 111
• Locations: 12 countries
• Sites: 23

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.

Conditions

Non-small Cell Lung Cancer

Keywords

PDR001; immunotherapy; Non-small cell lung cancer; lung; NSCLC

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (14)

• 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

Study Arms (4)

Group A: squamous, gem/cis+PDR001

EXPERIMENTAL

Drug: PDR001; Drug: Cisplatin; Drug: Gemcitabine

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

EXPERIMENTAL

Drug: PDR001; Drug: Cisplatin; Drug: Pemetrexed

Group C: paclitaxel/carbo+PDR001

EXPERIMENTAL

Drug: PDR001; Drug: Carboplatin; Drug: Paclitaxel

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

EXPERIMENTAL

Drug: PDR001; Drug: Cisplatin; Drug: Pemetrexed; Drug: Carboplatin; Drug: Canakinumab

Interventions

PDR001 DRUG

Powder for solution for infusion

Group A: squamous, gem/cis+PDR001; Group B: non-squamous, pem/cis+PDR001; Group C: paclitaxel/carbo+PDR001; Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab

Cisplatin DRUG

Intravenous infusion

Group A: squamous, gem/cis+PDR001; Group B: non-squamous, pem/cis+PDR001; Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab

Gemcitabine DRUG

Intravenous infusion

Group A: squamous, gem/cis+PDR001

Pemetrexed DRUG

Intravenous infusion

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

Carboplatin DRUG

Intravenous infusion

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

Paclitaxel DRUG

Intravenous infusion

Group C: paclitaxel/carbo+PDR001

Canakinumab DRUG

Subcutaneous injection

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

UCLA Santa Monica Hematology / Oncology SC-2

Santa Monica, California, 90404, United States

Location

Stanford Cancer Center SC

Stanford, California, 94305, United States

Location

Henry Ford Health System SC

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine SC

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Roeselare, 8800, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Prague, 140 59, Czechia

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Cologne, 51109, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Pokfulam, Hong Kong, Hong Kong

Location

Novartis Investigative Site

Meldola, FC, 47014, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Aviano, PN, 33081, Italy

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Related Publications (1)

• Santoro A, Pilar G, Tan DSW, Zugazagoitia J, Shepherd FA, Bearz A, Barlesi F, Kim TM, Overbeck TR, Felip E, Cai C, Eddy S, McCulloch T, Schaefer ES. Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC. BMC Cancer. 2024 Oct 24;24(1):1307. doi: 10.1186/s12885-024-12841-2.

  PMID: 39448966 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

spartalizumab; Cisplatin; Gemcitabine; Pemetrexed; Carboplatin; Paclitaxel; canakinumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: February 27, 2017
• Study Start: May 24, 2017
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: August 15, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); BE (2); SG (1); CA (1); ES (3); DE (2); FR (2); KR (1); CZ (1); HK (1); NL (1); IT (3)