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Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell CarcinomaPhase 1NCT02890069

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

A Phase 1 study testing PDR001, LCL161 and Everolimus in people with Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 25 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PDR001, LCL161 and Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
298 participants
Where
25 sitesin 7 countries
Study dates
14 Oct 2016to 22 Feb 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 43Show fewer
  • 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.

Trial locations and contacts

25 sites in 7 countries.

25 sites in 7 countries

United States9 sites

  • The Regents of the University of Michigan

    Ann Arbor, Michigan, 48109

  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • UT Health San Antonio Mays Cancer Center

    San Antonio, Texas, 78229

  • UCLA Santa Monica Hematology / Oncology SC

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98105

  • Washington University Medical School SC

    St Louis, Missouri, 63110

Other trials in United States

Netherlands4 sites

  • Novartis Investigative Site

    Amsterdam, 1066 CX

  • Novartis Investigative Site

    Leiden, 2300 RC

  • Novartis Investigative Site

    Rotterdam, 3075 EA

  • Novartis Investigative Site

    Utrecht, 3584CX

Other trials in Netherlands

Germany3 sites

  • Novartis Investigative Site

    Jena, 07740

  • Novartis Investigative Site

    Ulm, 89081

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

Spain3 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Pamplona, Navarre, 31008

Other trials in Spain

United Kingdom3 sites

  • Novartis Investigative Site

    Manchester, M20 4BX

  • Novartis Investigative Site

    Oxford, OX3 7LJ

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

South Korea2 sites

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, 03080

Other trials in South Korea

Taiwan1 site

  • Novartis Investigative Site

    Taipei, 10002

Other trials in Taiwan

About this study

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)

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.

Being tested
PDR001, LCL161, Everolimus, Panobinostat, QBM076
Keywords
PDR001, CRC, TNBC, NSCLC, RCC, Immunomodulation, Biomarkers, Bayesian logistic regression model
Medical subject headings
Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Triple Negative Breast Neoplasms, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PDR001Biological

    anti-PD1 antibody

  • LCL161Drug

  • EverolimusDrug

    Also called RAD001

  • PanobinostatDrug

    Also called LBH589

  • QBM076Drug

  • HDM201Drug

Study groups in NCT02890069
Study groupRoleWhat they receive
CRC - PDR001 + LCL161ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: LCL161
NSCLC - PDR001 + LCL161ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: LCL161
TNBC - PDR001 + LCL161ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: LCL161
CRC - PDR001+ EverolimusExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Everolimus
NSCLC - PDR001+ EverolimusExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Everolimus
TNBC - PDR001+ EverolimusExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Everolimus
CRC - PDR001 + PanobinostatExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Panobinostat
NSCLC - PDR001 + PanobinostatExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Panobinostat
TNBC - PDR001 + PanobinostatExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Biological: PDR001; Drug: Panobinostat
CRC - PDR001 + QBM076ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Drug: QBM076
TNBC - PDR001 + QBM076ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Drug: QBM076
NSCLC- PDR001 + QBM076ExperimentalEnrollment to this combination arm is closed to further enrollment.
Receives: Drug: QBM076
CRC - PDR001 + HDM201ExperimentalDose escalation completed, expansion arm.
Receives: Drug: HDM201
RCC - PDR001 + HDM201ExperimentalDose escalation completed, expansion arm.
Receives: Drug: HDM201

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    During the first two cycles Cycle = 28 days

    Measured: 5.5 years

  2. Frequency of dose interruptions and reductions

    Through study completion, an average of 6 months

    Measured: 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

    Measured: 6 years

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

    Through study completion, an average of 6 months

    Measured: 6 years

  5. Dose intensities

    Through study completion, an average of 6 months

    Measured: 6 years

Secondary outcomes (25)

  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

    Measured: 6 years

  2. Best overall response (BOR)

    per RECIST v1.1

    Measured: 6 years

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

    Measured: 6 years

  4. Presence of anti-PDR001 antibodies

    Measured: 6 years

  5. Progression free survival (PFS)

    per RECIST v1.1

    Measured: 6 years

  6. Treatment Free Survival (TFS)

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 6 years

  10. Concentration of anti-PDR001 antibodies

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

    Measured: 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

    Measured: 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

    Measured: 6 years

  13. Progression free survival (PFS) per irRC

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2016 (estimated)
  2. Study start14 Oct 2016
  3. Primary completion22 Feb 2022
  4. Study completion22 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
298 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02890069
Sponsor's protocol ID
CPDR001X2102
Status last verified
Jan 2023
First submitted
9 May 2016
Last updated
11 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PDR001, LCL161 and Everolimus in people with Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 25 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Netherlands, Germany, Spain, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Incidence of dose limiting toxicities (DLTs) (time frame: 5.5 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02890069.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.

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