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

Novartis

Status and phase: Terminated; Phase 1

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Gemcitabine; Drug: Paclitaxel; Drug: Carboplatin; Drug: Canakinumab; Drug: Cisplatin; Drug: Pemetrexed; Drug: PDR001

Study type: Interventional

Funder types: Industry

Identifiers

NCT03064854

CPDR001C2101

2016-002815-17 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 111 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 4 patient groups

Group A: squamous, gem/cis+PDR001

Experimental group

Treatment:

Drug: PDR001

Drug: Gemcitabine

Drug: Cisplatin

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

Experimental group

Treatment:

Drug: Pemetrexed

Drug: PDR001

Drug: Cisplatin

Group C: paclitaxel/carbo+PDR001

Experimental group

Treatment:

Drug: PDR001

Drug: Paclitaxel

Drug: Carboplatin

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

Experimental group

Treatment:

Drug: Pemetrexed

Drug: PDR001

Drug: Canakinumab

Drug: Carboplatin

Drug: Cisplatin