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Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03891953
Recruitment Status : Recruiting
First Posted : March 27, 2019
Last Update Posted : May 27, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a phase I/Ib, open label study. The escalation portion will characterize the safety and tolerability of DKY709 and DKY709 in combination with PDR001 in subjects with NSCLC or melanoma who have received prior anti-PD-1/PD-L1 therapy, or subjects with NPC. After the determination of the MTD/RD for a particular treatment arm, dose expansion will further assess safety, tolerability, PK/PD, and anti-tumor activity of each regimen at the MTD/RD.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Melanoma Nasopharyngeal Carcinoma Microsatellite Stable Colorectal Cancer Triple Negative Breast Cancer Drug: DKY709 Drug: PDR001 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/Ib, Open-label, Multi-center, Study of DKY709 as a Single Agent and in Combination With PDR001 in Patients With Advanced Solid Tumors
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : April 15, 2024
Estimated Study Completion Date : April 15, 2024


Arm Intervention/treatment
Experimental: DKY709
DKY709 monotherapy
Drug: DKY709
Novel immunomodulatory agent

Experimental: DKY709 + PDR001
Combination therapy with DKY709 and PDR001
Drug: DKY709
Novel immunomodulatory agent

Drug: PDR001
PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2
Other Name: Spartalizumab




Primary Outcome Measures :
  1. Safety of DKY709 single agent treatment or DKY709 in combination with PDR001. [ Time Frame: 24 months ]
    Incidence and severity of AEs and SAEs

  2. incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 1 Month ]
    The incidence of DLTs during the first cycle of treatment with single agent DKY709 or the combination of DKY709 with PDR001.

  3. Tolerability of DKY709 single agent treatment or DKY709 in combination with PDR001. [ Time Frame: 24 months ]
    Incidence and severity of AEs and SAEs


Secondary Outcome Measures :
  1. AUC of DKY709 and PDR001 [ Time Frame: 24 months ]
    AUC

  2. Cmax of DKY709 and PDR001 [ Time Frame: 24 months ]
    Cmax

  3. Tmax of DKY709 and PDR001 [ Time Frame: 24 months ]
    Tmax

  4. Half-life of DKY709 and PDR001 [ Time Frame: 24 months ]
    Half-life

  5. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    Determine PFS in each part of the study

  6. Best Overall Response (BOR) [ Time Frame: 24 months ]
    Determine BOR in each part of the study

  7. Duration of Response (DOR) [ Time Frame: 24 months ]
    Determine DOR in each part of the study

  8. Time to Progression (TTP) [ Time Frame: 24 months ]
    Determine TTP in each part of the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Patients must be ≥18 years of age at the time of informed consent form (ICF) signature.
  3. Patients with advanced/metastatic cancer who have progressed despite having received standard therapy in the metastatic setting or are intolerant to standard therapy, and for whom no effective standard therapy is available
  4. In expansion: patient with measurable disease as determined by RECIST version 1.1,
  5. Dose escalation, patients must fit into one of the following groups:

    • NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
    • Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy
    • NPC

    Dose expansion part, patients must fit into one of the following groups:

    • NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive disease after having experienced at least 4 months of investigator-assessed disease stability or response on prior anti-PD-L1-containing therapy
    • Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients should have documented progression following anti-PD-1/PD-L1 therapy.
    • NPC, naive to anti-PD-1/PD-L1 therapy
    • mssCRC, naive to anti-PD-1/PD-L1 therapy
    • TNBC, naive to anti-PD-1/PD-L1 therapy
  6. ECOG Performance Status ≤ 1
  7. Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis.

Exclusion Criteria:

  1. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated brain metastases should be neurologically stable for at least 4 weeks prior to study entry and off steroids for at least 2 weeks before administration of any study treatment.
  2. History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.
  3. Patient with out of range laboratory values defined as:

    • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 mL/min
    • Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
    • Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT > 5 x ULN
    • Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST > 5 x ULN
    • Absolute neutrophil count (ANC) < 1.0 x 109/L
    • Platelet count < 75 x 109/L (growth factor or transfusion support may not be used to meet entry criterion)
    • Hemoglobin (Hgb) < 8 g/dL (growth factor or transfusion support may not be used to meet entry criterion)
    • Magnesium, calcium or phosphate abnormality CTCAE > grade 1
    • Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable
  4. Clinically significant cardiac disease or impaired cardiac function, including any of the following:

    • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
    • On screening: QTcF > 450 msec (male), or > 460 msec (female)
    • QTc not assessable
    • Congenital long QT syndrome
    • History of familial long QT syndrome or known family history of as Torsades de Pointes
    • Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03891953


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Massachusetts
Massachusetts General Hospital Massachusetts Gen Hosp Recruiting
Boston, Massachusetts, United States, 02114
Contact: Michael Cournoyer       MCOURNOYER@mgh.harvard.edu   
Principal Investigator: Justin Gainor         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Israel Adam    617-632-3902    IsraelJ_Adam@dfci.harvard.edu   
Principal Investigator: Mark Awad         
United States, Tennessee
Sarah Cannon Research Institute Drug Ship - 3 Recruiting
Nashville, Tennessee, United States, 37203
Contact: Menka Talidis    615-329-7294    menka.talidis@sarahcannon.com   
Principal Investigator: Howard A Burris III         
Germany
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Hong Kong
Novartis Investigative Site Recruiting
Shatin, New Territories, Hong Kong
Japan
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104 0045
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03891953    
Other Study ID Numbers: CDKY709A12101C
2018-002580-26 ( EudraCT Number )
First Posted: March 27, 2019    Key Record Dates
Last Update Posted: May 27, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-small Cell Lung Cancer
Melanoma
Nasopharyngeal Carcinoma
Microsatellite Stable Colorectal Cancer
Triple Negative Breast Cancer
Additional relevant MeSH terms:
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Carcinoma
Colorectal Neoplasms
Melanoma
Triple Negative Breast Neoplasms
Nasopharyngeal Carcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms