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CompletedNCT02890069Updated Jan 11, 2023

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

A Phase 1 interventional study of PDR001 and LCL161 in Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma, sponsored by Novartis Pharmaceuticals. Completed at 25 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-01-11.

Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Feb 2022, 4 years 7 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
298
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma

Keywords

  • PDR001
  • CRC
  • TNBC
  • NSCLC
  • RCC
  • Immunomodulation
  • Biomarkers
  • Bayesian logistic regression model
03

In context

Carcinoma, Renal Cell

1,965 studies on the registry are indexed under Carcinoma, Renal Cell; 377 are open to participants now.

This study's enrollment of 298 is above the median of 42 across 1,479 interventional studies indexed under Carcinoma, Renal Cell.

Browse Carcinoma, Renal Cell studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
298 participants (actual)

Study arms

  • Experimental
    CRC - PDR001 + LCL161

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: LCL161

  • Experimental
    NSCLC - PDR001 + LCL161

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: LCL161

  • Experimental
    TNBC - PDR001 + LCL161

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: LCL161

  • Experimental
    CRC - PDR001+ Everolimus

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Everolimus

  • Experimental
    NSCLC - PDR001+ Everolimus

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Everolimus

  • Experimental
    TNBC - PDR001+ Everolimus

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Everolimus

  • Experimental
    CRC - PDR001 + Panobinostat

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Panobinostat

  • Experimental
    NSCLC - PDR001 + Panobinostat

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Panobinostat

  • Experimental
    TNBC - PDR001 + Panobinostat

    Enrollment to this combination arm is closed to further enrollment.

    Biological: PDR001 · Drug: Panobinostat

  • Experimental
    CRC - PDR001 + QBM076

    Enrollment to this combination arm is closed to further enrollment.

    Drug: QBM076

  • Experimental
    TNBC - PDR001 + QBM076

    Enrollment to this combination arm is closed to further enrollment.

    Drug: QBM076

  • Experimental
    NSCLC- PDR001 + QBM076

    Enrollment to this combination arm is closed to further enrollment.

    Drug: QBM076

  • Experimental
    CRC - PDR001 + HDM201

    Dose escalation completed, expansion arm.

    Drug: HDM201

  • Experimental
    RCC - PDR001 + HDM201

    Dose escalation completed, expansion arm.

    Drug: HDM201

Interventions

  • BiologicalPDR001

    anti-PD1 antibody

  • DrugLCL161
  • DrugEverolimus

    Also known as: RAD001

  • DrugPanobinostat

    Also known as: LBH589

  • DrugQBM076
  • DrugHDM201
06

What researchers measure

Primary outcomes

  1. Phase 1: Incidence of dose limiting toxicities (DLTs)

    During the first two cycles Cycle = 28 days

    Time frame: 5.5 years

  2. Frequency of dose interruptions and reductions

    Through study completion, an average of 6 months

    Time frame: 5.5 years

  3. Frequency and severity of treatment-emergent adverse events (AEs) and serious adverse events (SAEs)

    Through study completion, an average of 6 months

    Time frame: 6 years

  4. Changes between baseline and post-baseline laboratory parameters and vital signs

    Through study completion, an average of 6 months

    Time frame: 6 years

  5. Dose intensities

    Through study completion, an average of 6 months

    Time frame: 6 years

Secondary outcomes

  1. Changes from baseline in ECG parameters in patients recieving PDR001 in combination with Panobinostat

    Baseline and end of treatment, an average of 6 months

    Time frame: 6 years

  2. Best overall response (BOR)

    per RECIST v1.1

    Time frame: 6 years

  3. Time to reach max concentration (Tmax) for PDR001

    Time frame: 6 years

  4. Presence of anti-PDR001 antibodies

    Time frame: 6 years

  5. Progression free survival (PFS)

    per RECIST v1.1

    Time frame: 6 years

  6. Treatment Free Survival (TFS)

    Time frame: 6 years

  7. Maximum and minimum plasma concentrations of LCL161 (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  8. Maximum and minimum Plasma concentrations of everolimus (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  9. Maximum and minimum plasma concentrations of panobinostat (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  10. Concentration of anti-PDR001 antibodies

    Cycle 1 through cycle 6 in treatment period 1 and 2, an average of 6 months

    Time frame: 6 years

  11. Maximum and minimum serum concentration of PDR001 (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1 and 2, an average of 6 months

    Time frame: 6 years

  12. Area under the concentration-time curve calculated to the last concentration point (AUClast) for PDR001, as applicable

    Cycle 1 through cycle 6 in treatment period 1 and 2, an average of 6 months

    Time frame: 6 years

  13. Progression free survival (PFS) per irRC

    Time frame: 6 years

  14. Area under the concentration-time curve calculated to the last concentration point (AUClast) for LCL161, as applicable

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  15. Time to reach max concentration (Tmax) for LCL161

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  16. Time to reach max concentration (Tmax) for Everolimus

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  17. Time to reach max concentration (Tmax) for Panobinostat

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  18. Area under the concentration-time curve calculated to the last concentration point (AUClast) for Everolimus, as applicable

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  19. Area under the concentration-time curve calculated to the last concentration point (AUClast) for Panobinostat, as applicable

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  20. Maximum and minimum Plasma concentrations of QBM076 (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  21. Maximum and minimum Plasma concentrations of HDM201 (Cmax and Cmin)

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  22. Time to reach max concentration (Tmax) for QBM076

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  23. Time to reach max concentration (Tmax) for HDM201

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  24. Area under the concentration-time curve calculated to the last concentration point (AUClast) for QBM076, as applicable

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

  25. Area under the concentration-time curve calculated to the last concentration point (AUClast) for HDM201, as applicable

    Cycle 1 through cycle 6 in treatment period 1, an average of 6 months

    Time frame: 6 years

07

Study locations

25 sites
  • UCLA Santa Monica Hematology / Oncology SC
    Santa Monica, California 90404, United States
  • Sidney Kimmel Comprehensive Cancer Center
    Baltimore, Maryland 21231, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • The Regents of the University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Washington University Medical School SC
    Saint Louis, Missouri 63110, United States
  • University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • UT Health San Antonio Mays Cancer Center
    San Antonio, Texas 78229, United States
  • Huntsman Cancer Institute
    Salt Lake City, Utah 84112, United States
  • Seattle Cancer Care Alliance
    Seattle, Washington 98105, United States
  • Novartis Investigative Site
    Jena, 07740, Germany
  • Novartis Investigative Site
    Ulm, 89081, Germany
  • Novartis Investigative Site
    Wuerzburg, 97080, Germany
  • Novartis Investigative Site
    Seoul, Korea 05505, Korea, Republic of
  • Novartis Investigative Site
    Seoul, 03080, Korea, Republic of
  • Novartis Investigative Site
    Amsterdam, 1066 CX, Netherlands
  • Novartis Investigative Site
    Leiden, 2300 RC, Netherlands
  • Novartis Investigative Site
    Rotterdam, 3075 EA, Netherlands
  • Novartis Investigative Site
    Utrecht, 3584CX, Netherlands
  • Novartis Investigative Site
    Barcelona, Catalunya 08035, Spain
  • Novartis Investigative Site
    Pamplona, Navarra 31008, Spain
  • Novartis Investigative Site
    Madrid, 28041, Spain
  • Novartis Investigative Site
    Taipei, 10002, Taiwan
  • Novartis Investigative Site
    Sutton, Surrey SM2 5PT, United Kingdom
  • Novartis Investigative Site
    Manchester, M20 4BX, United Kingdom
  • Novartis Investigative Site
    Oxford, OX3 7LJ, United Kingdom
08

References and documents

Related links

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 11, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02890069
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 7, 2016
Start date
Oct 14, 2016
Primary completion
Feb 22, 2022
Completion
Feb 22, 2022
Last update
Jan 11, 2023

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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