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Phase I/II Study of PDR001 in Patients With Advanced Malignancies | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Phase I/II Study of PDR001 in Patients With Advanced Malignancies

Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies

NCT02404441•Novartis Pharmaceuticals

View on ClinicalTrials.gov

Summary

The purpose of this "first-in-human" study of PDR001 was 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.

Detailed Description

This study was 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. Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups. PDR001 was administered every 2 weeks until patient experienced unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment was discontinued at the discretion of the investigator or the patient.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Written informed consent must have been 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
+5 more 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).
+2 more criteria

Locations (41)

The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Oregon Health and Science University SC-10

Portland, Oregon, United States

Sarah Cannon Research Institute SCRI RC

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center MD Anderson PSC

Houston, Texas, United States

Huntsman Cancer Institute Univ. of Utah HCI

Salt Lake City, Utah, United States

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Paris, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Villejuif, France

Key Dates

Start Date

April 27, 2015

Primary Completion Date

July 21, 2020

Completion Date

July 21, 2020

Last Updated

August 3, 2022

Enrollment

319

ACTUAL participants

Conditions

MelanomaNon-small Sell Lung Cancer (NSCLC)Triple Negative Breast CancerAnaplastic Thyroid CancerOther Solid Tumors

Interventions

PDR001

BIOLOGICAL

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: August 3, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase I/II Study of PDR001 in Patients With Advanced Malignancies

Inclusion Criteria

Exclusion Criteria

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