A Study of PDR001 in Combination With LCL161, Everolimus or Panobinostat

Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacodynamics (PD) of PDR001 in Combination With LCL161, Everolimus (RAD001) or Panobinostat (LBH589)

ClinicalTrials.gov Identifier: NCT02890069

Novartis Reference Number: CPDR001X2102

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to combine the PDR001 checkpoint inhibitor with several agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.

Condition 
Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma
Phase 
Phase 1
Overall status 
Recruiting
Enrollment count 
315 participants
Start date 
Oct 14, 2016
Completion date 
May 28, 2021
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Biological
PDR001
anti-PD1 antibody
Drug
LCL161
Drug
Everolimus
Drug
Panobinostat
Drug
QBM076
Drug
HDM201

Eligibility Criteria

Inclusion Criteria:

Written informed consent prior to any procedure

Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to SOC, or for whom no standard therapy exists. Patients must fit into one of the following groups:

• CRC •NSCLC • TNBC• RCC

ECOG ≤ 2
Patient must have a site of disease for biopsy, and be a candidate for tumor biopsy according to the institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy on this study.
Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.

Exclusion Criteria:

Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy within prior 2 weeks.
Patients with known hypersensitivity to any of the components of an investigational treatment will be excluded from participation in the corresponding arm but are eligible for participation in other study arm; Patients that have a history of hypersensitivity to rapamycin derivatives will be excluded from participation in the everolimus arm
History of or current drug-induced interstitial lung disease or pneumonitis grade ≥2
Out of range lab values as defined in protocol
Impaired cardiac function or clinically significant cardiac disease
Active, known or suspected autoimmune disease
Human Immunodeficiency Virus (HIV), or active Hepatitis C (HCV) virus. Escalation: active Hepatitis B (HBV); Expansion: Patients with Chronic HBV currently on medication will not be excluded.
Impairment of gastrointestinal (GI) function
Malignant disease, other than that being treated in this study
Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity and washout period is 6 weeks; prior immunotherapy - washout is 4 weeks
Active infection requiring systemic antibiotic therapy.
Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids or treatment with low, stable dose of steroid (<10 mg/day prednisone or equivalent) for stable CNS metastatic disease.
Patients receiving systemic treatment with any immunosuppressive medication.
Major surgery within 2 weeks of the first dose of study treatment
Radiotherapy within 2 weeks of the first dose of study drug
Participation in an interventional, investigational study within 2 weeks of the first dose 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 therapy.
Use of hematopoietic colony stimulating growth factors </= 3 weeks prior to first dose

Additional exclusion criteria for PDR001/LCL161

Patients requiring medications metabolized through CYP3A4/5 and have a narrow therapeutic index or medications that are CYP3A4 substrates that cause QT prolongation
Patients requiring treatment with strong CYP2C8 inhibitors

Additional exclusion criteria for PDR001/Everolimus

Patients requiring treatment with moderate CYP3A4 inhibitors
Patients requiring treatment with a strong CYP3A4 inhibitor or inducer

Additional exclusion criteria for PDR001/Panobinostat-

Patient who received DAC inhibitors
Patient needing valproic acid during the study or within 5 days prior to first dose
Patients requiring medications that are sensitive CYP2D6 substrates areCYP2D6 substrates with a narrow therapeutic index or are anti-arrhythmic drugs/drugs with QT-prolongation risks
Patients requiring a strong inhibitor or inducer of CYP3A4
Clinically significant, uncontrolled heart disease and/or recent cardiac event within 6 months prior to study
Unresolved diarrhea ≥ CTCAE grade 2 or a medical condition associated with chronic diarrhea
Taking medications with QT prolongation risk or interval or inducing Torsade de pointes

Additional exclusion criteria for PDR001/QBM076-

Patients requiring medications that are strong inducers or strong inhibitors of CYP3A4
Patients requiring medications with narrow therapeutic index CYP3A4 substrates
Women using any form of hormonal contraception (oral, injected, implanted, transdermal) will be excluded (unless they are willing to switch to another effective form of contraception under their physician's guidance)

Additional exclusion criteria for PDR001/HDM201-

Prior treatment with compounds with the same mode of action as proposed for HDM201, i.e. an inhibition of the interaction of TP53 with HDM2, e.g. RG7112 or CGM097
Patients who require the following treatments moderate to strong CYP3A4 inhibitors; any substrates of CYP3A4/5 with a narrow therapeutic index
Moderate to strong CYP3A4 inducers
Patients having out of range values for:

Absolute neutrophil count (ANC) <1500/µL; Platelets < 100 000/µL

Other protocol-defined inclusion exclusion criteria may apply.

Study Locations

United States
UCLA Santa Monica Hematology / Oncology SC
Recruiting
Santa Monica, 90404
California
United States
Sidney Kimmel Comprehensive Cancer Center
Recruiting
Baltimore, 21231
Maryland
United States
Massachusetts General Hospital
Recruiting
Boston, 02114
Massachusetts
United States
The Regents of the University of Michigan
Recruiting
Ann Arbor, 48109
Michigan
United States
Washington University Medical School SC
Completed
Saint Louis, 63110
Missouri
United States
University of Texas MD Anderson Cancer Center
Completed
Houston, 77030
Texas
United States
UT Health San Antonio Mays Cancer Center
Recruiting
San Antonio, 78229
Texas
United States
Huntsman Cancer Institute
Completed
Salt Lake City, 84112
Utah
United States
Seattle Cancer Care Alliance
Recruiting
Seattle, 98105
Washington
United States
Germany
Novartis Investigative Site
Recruiting
Jena, 07740
-
Germany
Novartis Investigative Site
Recruiting
Ulm, 89081
-
Germany
Novartis Investigative Site
Recruiting
Wuerzburg, 97080
-
Germany
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
Korea
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Netherlands
Novartis Investigative Site
Recruiting
Amsterdam, 1066 CX
-
Netherlands
Novartis Investigative Site
Recruiting
Leiden, 2300 RC
-
Netherlands
Novartis Investigative Site
Recruiting
Rotterdam, 3075 EA
-
Netherlands
Novartis Investigative Site
Recruiting
Utrecht, 3584CX
-
Netherlands
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Pamplona, 31008
Navarra
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
United Kingdom
Novartis Investigative Site
Recruiting
Sutton, SM2 5PT
Surrey
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M20 9BX
-
United Kingdom
Novartis Investigative Site
Active, not recruiting
Oxford, OX3 7LJ
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

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