Summary

for people ages 18 years and up (full criteria)
at UCLA
study started
estimated completion:

Description

Summary

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.

Official Title

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)

Keywords

Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma PDR001 CRC TNBC NSCLC RCC Immunomodulation Biomarkers Bayesian logistic regression model Colorectal Neoplasms Adenocarcinoma Carcinoma, Renal Cell Triple Negative Breast Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung Kidney Neoplasms Panobinostat Everolimus Sirolimus LCL161 QBM076 HDM201 CRC - PDR001 + LCL161 NSCLC - PDR001 + LCL161 TNBC - PDR001 + LCL161 CRC - PDR001+ Everolimus NSCLC - PDR001+ Everolimus TNBC - PDR001+ Everolimus CRC - PDR001 + Panobinostat NSCLC - PDR001 + Panobinostat TNBC - PDR001 + Panobinostat CRC - PDR001 + QBM076 TNBC - PDR001 + QBM076 NSCLC- PDR001 + QBM076 CRC - PDR001 + HDM201 RCC - PDR001 + HDM201

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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.

You CAN'T join if...

  • 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.

Locations

  • Novartis Investigative Site accepting new patients
    Santa Monica California 90404 United States
  • Novartis Investigative Site accepting new patients
    Salt Lake City Utah 84112 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT02890069
Phase
Phase 1
Study Type
Interventional
Last Updated