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Trial details
Phase I/II Study of PDR001 in Patients With Advanced Malignancies
Current status:
Approved
|
Date registered:
15/10/2019
Trial version(s)
History: 20/02/2019
History: 20/02/2019
History: 20/02/2019
History: 20/02/2019
Current: 20/02/2019
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Main Information
Primary registry identifying number
LBCTR2019060201
Protocol number
CPDR001X2101
MOH registration number
7805/ص
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Retrospective
Type of registration: Justify
LCTR was recently initiated, original file was previously submitted by Paper
Date of registration in national regulatory agency
26/08/2016
Primary sponsor
Novartis Pharma Services Inc.
Primary sponsor: Country of origin
Novartis Pharmaceuticals
Public title
Phase I/II Study of PDR001 in Patients With Advanced Malignancies
Acronym
Scientific title
Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
Acronym
Brief summary of the study: English
The purpose of this "first-in-human" study of PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment is discontinued at the discretion of the investigator or the patient.
Brief summary of the study: Arabic
دراسة مفتوحة اللصاقة متعددة المراكز في المرحلتين الأولى والثانية حول سلامة وفعاليّة PDR001 المعطى للمرضى الذين يعانون من أورام خبيثة متقدّمة
Health conditions/problem studied: Specify
Patients with advanced malignancies : melanoma, NSCLC, TNBC and anaplastic thyroid cancer
Interventions: Specify
Biological: PDR001 anti-PD1 antibody
Key inclusion and exclusion criteria: Inclusion criteria
•Written informed consent must be obtained prior to any screening procedures •Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. •Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups: ◦Group 1a and 1b: NSCLC: Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab). Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence. •Group 2: Melanoma: All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents. •Group 3: Triple negatice breast cancer. •Group 4: Anaplastic thyroid cancer •Patients are not required to have received or progressed on a prior therapy. •Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease,). •Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient. ◦ECOG Performance Status ≤ 1. ◦Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
•History of severe hypersensitivity reactions to other mAbs •Subjects with active, known or suspected autoimmune disease. Subjects 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. •Active infection requiring systemic antibiotic therapy. •HIV infection. •Active HBV or HCV infection. •Patients with ocular melanoma. •Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks washout period. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 6 weeks is indicated as the washout period. •Prior PD-1- or PD-L1-directed therapy. •Patients requiring chronic treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are not prohibited. •Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above). •Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment. •Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy Other protocol defined Inclusion/Exclusion may apply.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Non-randomized controlled trial
Study design: Masking
Open (masking not used)
Study design: Control
Dose comparison
Study phase
1 to 2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
No
Name of IMP
PDR001
Type of IMP
Others
Type of IMP: Specify
Anti PDL 1
Pharmaceutical class
PDR001 is a humanized monoclonal antibody and is a high-affinity, ligand-blocking, humanized immunoglobulin G4 (IgG4) directed against PD-1 and blocks the binding of PD-L1 and PD-L2.
Therapeutic indication
PD-1 is a critical immune checkpoint receptor that is expressed on CD4 and CD8 T cells upon activation (Freeman 2008). Engagement of PD-1 by its ligands, PD-L1 and PD-L2, transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function (Riley 2009). During tumorigenesis, cancer cells from a wide range of tumor types exploit immune checkpoint pathways, such as PD-1/PD-L1, to avoid detection by the adaptive immune system (Murphy 2011). mAb inhibitors of immunological checkpoints, including PD-1 and PD-L1, have demonstrated significant antitumor activity in patients with various solid tumors with less toxicity than broad immune activators, such as interleukin-2 (IL-2) and Interferon-alpha (IFN-α) (Topalian et al 2012, Hamid et al 2013, Topalian et al 2014, Seiwert et al 2014).
Therapeutic benefit
Progression free survival
Biospecimen retention
Samples with DNA**
Biospecimen description
Samples for circulating tumor DNA will be shipped to central laboratory designated by Novartis.
Target sample size
3
Actual enrollment target size
3
Date of first enrollment: Type
Actual
Date of first enrollment: Date
10/01/2017
Date of study closure: Type
Actual
Date of study closure: Date
18/11/2020
Recruitment status
Complete
Date of completion
12/06/2017
IPD sharing statement plan
No
IPD sharing statement description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Additional data URL
https://clinicaltrials.gov/ct2/show/record/NCT02404441?term=PDR001&recrs=de&rank=4
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Clinicaltrials.gov
NCT02404441
Sources of Monetary or Material Support
Name
Novartis Pharma Services Inc.
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Joseph
Kattan
Beirut
Lebanon
03635913
jkattan62@hotmail.com
Hotel Dieu De France
Scientific
Hind
Khairallah
Sin El Fil
Lebanon
+961 1 512002 Ext. 271
Hind.Khairallah@fattal.com.lb
Khalil Fattal et Fils s.a.l.
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu De France
Joseph Kattan
Hematology Oncology
Approved
Bellevue Medical Center
Fadi El Karak
Hematology Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
06/04/2017
Nancy Alam
nancy.alam@usj.edu.lb
+961 (0) 1 421000 ext 2335
Bellevue Medical Center
02/10/2017
Ghassan Maalouf
gmaalouf@bmc.com.lb
+961 (0) 1 682666 ext 7600
Countries of Recruitment
Name
Lebanon
Canada
France
Germany
Hungary
Italy
Netherlands
Norway
Poland
Spain
Taiwan
United States of America
Turkey
Health Conditions or Problems Studied
Condition
Code
Keyword
NSCLC
Bronchus or lung, unspecified (C34.9)
NSCLC
Interventions
Intervention
Description
Keyword
ICF, medical history, demography, radiology, vital signs, IMP administration
ICF, medical history, demography, radiology, vital signs, IMP administration
ICF, medical history, demography, radiology, vital signs, IMP administration
Primary Outcomes
Name
Time points
Measure
Overall response Rate (ORR)
6 cycles
all patients have completed at least 6 cycles of treatment
Key Secondary Outcomes
Name
Time points
Measure
•Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity
Continuously
Continuously
•Overall Response Rate (ORR)
every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression
every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression
•Progression Free Survival (PFS)
every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression
every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial