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

NCT ID: NCT02890069

Last Updated: 2023-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 298 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-14
• Study Completion Date: 2022-02-22

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CRC - PDR001 + LCL161

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

LCL161

Intervention Type: DRUG

NSCLC - PDR001 + LCL161

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

LCL161

Intervention Type: DRUG

TNBC - PDR001 + LCL161

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

LCL161

Intervention Type: DRUG

CRC - PDR001+ Everolimus

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Everolimus

Intervention Type: DRUG

NSCLC - PDR001+ Everolimus

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Everolimus

Intervention Type: DRUG

TNBC - PDR001+ Everolimus

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Everolimus

Intervention Type: DRUG

CRC - PDR001 + Panobinostat

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Panobinostat

Intervention Type: DRUG

NSCLC - PDR001 + Panobinostat

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Panobinostat

Intervention Type: DRUG

TNBC - PDR001 + Panobinostat

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

anti-PD1 antibody

Panobinostat

Intervention Type: DRUG

CRC - PDR001 + QBM076

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

QBM076

Intervention Type: DRUG

TNBC - PDR001 + QBM076

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

QBM076

Intervention Type: DRUG

NSCLC- PDR001 + QBM076

Enrollment to this combination arm is closed to further enrollment.

Group Type: EXPERIMENTAL

QBM076

Intervention Type: DRUG

CRC - PDR001 + HDM201

Dose escalation completed, expansion arm.

Group Type: EXPERIMENTAL

HDM201

Intervention Type: DRUG

RCC - PDR001 + HDM201

Dose escalation completed, expansion arm.

Group Type: EXPERIMENTAL

HDM201

Intervention Type: DRUG

Interventions

PDR001

anti-PD1 antibody

Intervention Type: BIOLOGICAL

LCL161

Intervention Type: DRUG

Everolimus

Intervention Type: DRUG

Panobinostat

Intervention Type: DRUG

QBM076

Intervention Type: DRUG

HDM201

Intervention Type: DRUG

Other Intervention Names

RAD001; LBH589

Eligibility Criteria

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

• 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

• Patients requiring treatment with moderate CYP3A4 inhibitors
• Patients requiring treatment with a strong CYP3A4 inhibitor or inducer

• 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

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

UCLA Santa Monica Hematology / Oncology SC

Santa Monica, California, United States

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

The Regents of the University of Michigan

Ann Arbor, Michigan, United States

Washington University Medical School SC

St Louis, Missouri, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

UT Health San Antonio Mays Cancer Center

San Antonio, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Novartis Investigative Site

Jena, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Leiden, , Netherlands

Novartis Investigative Site

Rotterdam, , Netherlands

Novartis Investigative Site

Utrecht, , Netherlands

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Pamplona, Navarre, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Novartis Investigative Site

Manchester, , United Kingdom

Novartis Investigative Site

Oxford, , United Kingdom

Countries

United States; Germany; Netherlands; South Korea; Spain; Taiwan; United Kingdom

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18008

Study Results

Other Identifiers

CPDR001X2102

Identifier Type: -

Identifier Source: org_study_id