Breast Cancer Clinical Trial
A Study of PDR001 in Combination With LCL161, Everolimus or Panobinostat
The purpose of this study was 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.
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.
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.
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There are 25 Locations for this study
Santa Monica California, 90404, United States
Baltimore Maryland, 21231, United States
Boston Massachusetts, 02114, United States
Ann Arbor Michigan, 48109, United States
Saint Louis Missouri, 63110, United States
Houston Texas, 77030, United States
San Antonio Texas, 78229, United States
Salt Lake City Utah, 84112, United States
Seattle Washington, 98105, United States
Jena , 07740, Germany
Ulm , 89081, Germany
Wuerzburg , 97080, Germany
Seoul Korea, 05505, Korea, Republic of
Seoul , 03080, Korea, Republic of
Amsterdam , 1066 , Netherlands
Leiden , 2300 , Netherlands
Rotterdam , 3075 , Netherlands
Utrecht , 3584C, Netherlands
Barcelona Catalunya, 08035, Spain
Pamplona Navarra, 31008, Spain
Madrid , 28041, Spain
Taipei , 10002, Taiwan
Sutton Surrey, SM2 5, United Kingdom
Manchester , M20 4, United Kingdom
Oxford , OX3 7, United Kingdom
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