NCT02890069

Brief 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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
298

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Oct 2016

Longer than P75 for phase_1

Geographic Reach
7 countries

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 9, 2016

Completed
4 months until next milestone

First Posted

Study publicly available on registry

September 7, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

October 14, 2016

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 22, 2022

Completed
Last Updated

January 11, 2023

Status Verified

January 1, 2023

Enrollment Period

5.4 years

First QC Date

May 9, 2016

Last Update Submit

January 10, 2023

Conditions

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

Keywords

PDR001CRCTNBCNSCLCRCCImmunomodulationBiomarkersBayesian logistic regression model

Outcome Measures

Primary Outcomes (5)

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

    During the first two cycles Cycle = 28 days

    5.5 years

  • Frequency of dose interruptions and reductions

    Through study completion, an average of 6 months

    5.5 years

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

    Through study completion, an average of 6 months

    6 years

  • Changes between baseline and post-baseline laboratory parameters and vital signs

    Through study completion, an average of 6 months

    6 years

  • Dose intensities

    Through study completion, an average of 6 months

    6 years

Secondary Outcomes (25)

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

    6 years

  • Best overall response (BOR)

    6 years

  • Time to reach max concentration (Tmax) for PDR001

    6 years

  • Presence of anti-PDR001 antibodies

    6 years

  • Progression free survival (PFS)

    6 years

  • +20 more secondary outcomes

Study Arms (14)

CRC - PDR001 + LCL161

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: LCL161

NSCLC - PDR001 + LCL161

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: LCL161

TNBC - PDR001 + LCL161

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: LCL161

CRC - PDR001+ Everolimus

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Everolimus

NSCLC - PDR001+ Everolimus

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Everolimus

TNBC - PDR001+ Everolimus

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Everolimus

CRC - PDR001 + Panobinostat

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Panobinostat

NSCLC - PDR001 + Panobinostat

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Panobinostat

TNBC - PDR001 + Panobinostat

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Biological: PDR001Drug: Panobinostat

CRC - PDR001 + QBM076

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Drug: QBM076

TNBC - PDR001 + QBM076

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Drug: QBM076

NSCLC- PDR001 + QBM076

EXPERIMENTAL

Enrollment to this combination arm is closed to further enrollment.

Drug: QBM076

CRC - PDR001 + HDM201

EXPERIMENTAL

Dose escalation completed, expansion arm.

Drug: HDM201

RCC - PDR001 + HDM201

EXPERIMENTAL

Dose escalation completed, expansion arm.

Drug: HDM201

Interventions

PDR001BIOLOGICAL

anti-PD1 antibody

CRC - PDR001 + LCL161CRC - PDR001 + PanobinostatCRC - PDR001+ EverolimusNSCLC - PDR001 + LCL161NSCLC - PDR001 + PanobinostatNSCLC - PDR001+ EverolimusTNBC - PDR001 + LCL161TNBC - PDR001 + PanobinostatTNBC - PDR001+ Everolimus
LCL161DRUG
CRC - PDR001 + LCL161NSCLC - PDR001 + LCL161TNBC - PDR001 + LCL161
EverolimusDRUG
Also known as: RAD001
CRC - PDR001+ EverolimusNSCLC - PDR001+ EverolimusTNBC - PDR001+ Everolimus
PanobinostatDRUG
Also known as: LBH589
CRC - PDR001 + PanobinostatNSCLC - PDR001 + PanobinostatTNBC - PDR001 + Panobinostat
QBM076DRUG
CRC - PDR001 + QBM076NSCLC- PDR001 + QBM076TNBC - PDR001 + QBM076
HDM201DRUG
CRC - PDR001 + HDM201RCC - PDR001 + HDM201

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 may not qualify 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
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

UCLA Santa Monica Hematology / Oncology SC

Santa Monica, California, 90404, United States

Location

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The Regents of the University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University Medical School SC

St Louis, Missouri, 63110, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UT Health San Antonio Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Jena, 07740, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Leiden, 2300 RC, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Utrecht, 3584CX, Netherlands

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 4BX, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Colorectal NeoplasmsCarcinoma, Non-Small-Cell LungAdenocarcinomaTriple Negative Breast NeoplasmsCarcinoma, Renal Cell

Interventions

spartalizumabLCL161EverolimusPanobinostatsiremadlin

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeBreast NeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic ChemicalsHydroxamic AcidsHydroxylaminesAminesHydroxy AcidsCarboxylic AcidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 9, 2016

First Posted

September 7, 2016

Study Start

October 14, 2016

Primary Completion

February 22, 2022

Study Completion

February 22, 2022

Last Updated

January 11, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

KR(2)US(9)TW(1)NL(4)DE(3)ES(3)GB(3)