Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
CRC - PDR001 + LCL161
Dose escalation completed; expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: LCL161
Experimental
NSCLC - PDR001 + LCL161
Dose escalation completed, expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: LCL161
Experimental
TNBC - PDR001 + LCL161
Dose escalation completed, expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: LCL161
Experimental
CRC - PDR001+ Everolimus
Dose escalation completed, expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Everolimus
    Other names:
    • RAD001
Experimental
NSCLC - PDR001+ Everolimus
Dose escalation completed, expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Everolimus
    Other names:
    • RAD001
Experimental
TNBC - PDR001+ Everolimus
Dose escalation completed, expansion arm.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Everolimus
    Other names:
    • RAD001
Experimental
CRC - PDR001 + Panobinostat
Enrollment to this combination arm is closed to further enrollment.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Panobinostat
    Other names:
    • LBH589
Experimental
NSCLC - PDR001 + Panobinostat
Enrollment to this combination arm is closed to further enrollment.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Panobinostat
    Other names:
    • LBH589
Experimental
TNBC - PDR001 + Panobinostat
Enrollment to this combination arm is closed to further enrollment.
  • Biological: PDR001
    anti-PD1 antibody
  • Drug: Panobinostat
    Other names:
    • LBH589
Experimental
CRC - PDR001 + QBM076
Dose escalation.
  • Drug: QBM076
Experimental
TNBC - PDR001 + QBM076
Dose escalation.
  • Drug: QBM076
Experimental
NSCLC- PDR001 + QBM076
Dose escalation.
  • Drug: QBM076
Experimental
CRC - PDR001 + HDM201
Dose escalation.
  • Drug: HDM201
Experimental
RCC - PDR001 + HDM201
Dose escalation.
  • Drug: HDM201

Recruiting Locations

Novartis Investigative Site
San Antonio, Texas 78229
Contact:
Ofelia Romero
210-450-1286
romeroo@uthscsa.edu

More Details

NCT ID
NCT02890069
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
Novartis.email@novartis.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.