A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)

NCT ID: NCT02900664

Last Updated: 2022-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 283 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-23
• Study Completion Date: 2021-03-17

Brief Summary

The purpose of this study was to combine the PDR001 checkpoint inhibitor with each of four 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.

Detailed Description

This was a Phase Ib, multi-center, open-label study, to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 in combination with canakinumab, CJM112, trametinib and EGF816 and single agent (s.a.) canakinumab in subjects with Triple Negative Breast Cancer (TNBC), Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC). The study comprised a dose escalation part for combination treatments only, followed by a dose expansion part.

Conditions

Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma

Study Design

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

Study Groups

PDR + ACZ 100mg Q8W

PDR + ACZ 100mg Q8W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

PDR + ACZ 300mg Q8W

PDR + ACZ 300mg Q8W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

PDR + ACZ RDE TNBC

PDR + ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

PDR + ACZ RDE NSCLC

PDR + ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

PDR + ACZ RDE CRC

PDR + ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

PDR + CJM 25mg Q4W

PDR + CJM 25mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 75mg Q4W

PDR + CJM 75mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 225mg Q4W

PDR + CJM 225mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 450mg Q4W

PDR + CJM 450mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 450mg Q2W

PDR + CJM 450mg Q2W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 900mg Q4W

PDR + CJM 900mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 900mg Q2W

PDR + CJM 900mg Q2W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + CJM 1200mg Q4W

PDR + CJM 1200mg Q4W

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

CJM112

Intervention Type: BIOLOGICAL

Solution for infusion

PDR + TMT 0.5mg QD

PDR + TMT 0.5mg QD

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

TMT212

Intervention Type: DRUG

Tablets

PDR + TMT 1mg QD

PDR + TMT 1mg QD

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

TMT212

Intervention Type: DRUG

Tablets

PDR + TMT 1mg QD, 3 Weeks on/1 Week off

PDR + TMT 1mg QD, 3 Weeks on/1 Week off

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

TMT212

Intervention Type: DRUG

Tablets

PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off

PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

TMT212

Intervention Type: DRUG

Tablets

PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off

PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off

Group Type: EXPERIMENTAL

PDR001

Intervention Type: BIOLOGICAL

Powder for solution for infusion

TMT212

Intervention Type: DRUG

Tablets

PDR + EGF816 25mg QD

PDR + EGF816 25mg QD

Group Type: EXPERIMENTAL

EGF816

Intervention Type: DRUG

Tablets

PDR + EGF816 50mg QD

PDR + EGF816 50mg QD

Group Type: EXPERIMENTAL

EGF816

Intervention Type: DRUG

Tablets

s.a. ACZ RDE TNBC

Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)

Group Type: EXPERIMENTAL

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

s.a. ACZ RDE NSCLC

Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)

Group Type: EXPERIMENTAL

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

s.a. ACZ RDE CRC

Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)

Group Type: EXPERIMENTAL

ACZ885

Intervention Type: BIOLOGICAL

Solution for injection

Interventions

PDR001

Powder for solution for infusion

Intervention Type: BIOLOGICAL

ACZ885

Solution for injection

Intervention Type: BIOLOGICAL

CJM112

Solution for infusion

Intervention Type: BIOLOGICAL

TMT212

Tablets

Intervention Type: DRUG

EGF816

Tablets

Intervention Type: DRUG

Other Intervention Names

Spartalizumab/PDR001; canakinumab; trametinib; Nazartinib

Eligibility Criteria

Inclusion Criteria

• 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 standard therapy, and for whom no effective therapy is available.

Patients must fit into one of the following groups:

• Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
• Non-small cell lung cancer (NSCLC) (adenocarcinoma)
• Triple Negative Breast Cancer (TNBC) (D
• ECOG Performance Status ≤ 2
• Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, 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.
• Written informed consent must be obtained prior to any screening procedures other than procedures performed as part of standard of care.

Exclusion Criteria

• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
• Impaired cardiac function or clinically significant cardiac disease.
• Patients with active, known or suspected autoimmune disease.
• Human Immunodeficiency Virus infection at screening.
• Escalation part: Active Hepatitis B (HBV) or Hepatitis C (HCV) virus infection at screening.

Expansion part: Patients with active HBV or HCV are excluded, excepting those patients undergoing treatment for HBV or HCV.

• Malignant disease, other than that being treated in this study.
• Recent systemic anti-cancer therapy
• Active infection requiring systemic antibiotic therapy.
• Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency or treatment with low, stable dose of steroid (<10mg/ day prednisone or equivalent) for stable CNS metastatic disease.
• Patients receiving systemic treatment with any immunosuppressive medication, excepting the above
• Use of any live vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
• Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
• Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
• Recent use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF)

• Patients with tuberculosis (TB). Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
• Patients who have been infected with HBV or HCV including those with inactive disease.

• Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
• Patients with history of and/or active inflammatory bowel disease.
• Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
• Active candida infection, including mucocutaneous infection or history of invasive candidiasis.

• Patients with history of retinal vein oclusion.
• Patients with history of interstitial lung disease or pneumonitis.
• Patients with cardiomyopathy and/or LVEF < LLN.
• Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners.
• Hemoglobin (Hgb) < 9 g/dL without growth factor or transfusion support
• Women of child-bearing potential using hormonal contraception, unless an additional contraception method is also used according to the Mekinist® label.

• NSCLC patients with EGFR mutant tumors.
• Strong inhibitors and strong inducers of CYP3A4 should not be used concomitantly.
• Patients with history of interstitial lung disease.
• Patients who have been infected with HBV or HCV including those with inactive disease.
• Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners
• Patients cannot have received radiotherapy to lung fields within 6 months of study treatment start.

• 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

Sidney Kimmel Comprehensive Cancer Center SC-3

Baltimore, Maryland, United States

Dana Farber Cancer Center

Boston, Massachusetts, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Wilrijk, , Belgium

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Villejuif, , France

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Tainan City, , Taiwan

Novartis Investigative Site

Taoyuan District, , Taiwan

Countries

United States; Belgium; Canada; France; Israel; Italy; Singapore; Spain; Taiwan

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17917

Results for CPDR001X2103 from the Novartis Clinical Trials Website

Other Identifiers

2016-000633-49

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPDR001X2103

Identifier Type: -

Identifier Source: org_study_id