Breast Cancer Clinical Trial

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

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.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

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
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.

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

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

319

Study ID:

NCT02404441

Recruitment Status:

Completed

Sponsor:

Novartis Pharmaceuticals

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There are 41 Locations for this study

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The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins
Baltimore Maryland, 21287, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Oregon Health and Science University SC-10
Portland Oregon, 97239, United States
Sarah Cannon Research Institute SCRI RC
Nashville Tennessee, 37203, United States
University of Texas MD Anderson Cancer Center MD Anderson PSC
Houston Texas, 77030, United States
Huntsman Cancer Institute Univ. of Utah HCI
Salt Lake City Utah, 84112, United States
Novartis Investigative Site
Toronto Ontario, M5G 1, Canada
Novartis Investigative Site
Paris Cedex 10 , 75475, France
Novartis Investigative Site
Toulouse Cedex 9 , 31059, France
Novartis Investigative Site
Villejuif Cedex , 94800, France
Novartis Investigative Site
Essen , 45147, Germany
Novartis Investigative Site
Jena , 07740, Germany
Novartis Investigative Site
Ulm , 89081, Germany
Novartis Investigative Site
Budapest , 1134, Hungary
Novartis Investigative Site
Debrecen , 4032, Hungary
Novartis Investigative Site
Bologna BO, 40138, Italy
Novartis Investigative Site
Milano MI, 20132, Italy
Novartis Investigative Site
Rozzano MI, 20089, Italy
Novartis Investigative Site
Modena MO, 41124, Italy
Novartis Investigative Site
Napoli , 80131, Italy
Novartis Investigative Site
Ashrafieh , 16683, Lebanon
Novartis Investigative Site
Amsterdam , 1066 , Netherlands
Novartis Investigative Site
Leiden , 2300 , Netherlands
Novartis Investigative Site
Oslo , 0310, Norway
Novartis Investigative Site
Gdansk , 80 95, Poland
Novartis Investigative Site
Poznan , 60-69, Poland
Novartis Investigative Site
Rzeszow , 35-02, Poland
Novartis Investigative Site
Warszawa , 02 78, Poland
Novartis Investigative Site
Barcelona Catalunya, 08035, Spain
Novartis Investigative Site
Madrid , 28034, Spain
Novartis Investigative Site
Madrid , 28041, Spain
Novartis Investigative Site
Madrid , 28050, Spain
Novartis Investigative Site
Tainan Taiwan ROC, 70403, Taiwan
Novartis Investigative Site
Taipei , 10002, Taiwan
Novartis Investigative Site
Songkhla Hat Yai, 90110, Thailand
Novartis Investigative Site
Bangkok , 10330, Thailand
Novartis Investigative Site
Adana , 01250, Turkey
Novartis Investigative Site
Edirne , 22030, Turkey
Novartis Investigative Site
Istanbul , 34303, Turkey
Novartis Investigative Site
Istanbul , 34890, Turkey
Novartis Investigative Site
Izmir , 35040, Turkey

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

319

Study ID:

NCT02404441

Recruitment Status:

Completed

Sponsor:


Novartis Pharmaceuticals

How clear is this clinincal trial information?

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