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

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

ClinicalTrials.gov Identifier: NCT03891953

Novartis Reference Number: CDKY709A12101C

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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 
Carcinoma, Non-Small-Cell Lung
Melanoma
Nasopharyngeal Carcinoma
Microsatellite Stable Colorectal Cancer
Triple Negative Breast Cancer
Phase 
Phase 1
Overall status 
Recruiting
Enrollment count 
320 participants
Start date 
May 07, 2019
Completion date 
Apr 14, 2023
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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

Eligibility Criteria

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Patients must be ≥18 years of age at the time of informed consent form (ICF) signature.
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
In expansion: patient with measurable disease as determined by RECIST version 1.1,

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

NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
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, primarily refractory to anti-PD-1/PD-L1 therapy with documented PD-L1 ≥ 1%
Melanoma, primarily refractory to 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 Primarily refractory is defined as duration of therapy with a regimen which includes an anti-PD-1/PD-L1 agent ≤ 6 months prior to disease progression and no objective evidence of significant radiologic response during treatment.
ECOG Performance Status ≤ 2
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.

Exclusion Criteria:

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.
History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.

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)
Potassium, magnesium, calcium or phosphate abnormality CTCAE > grade 1

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

Study Locations

United States
Dana Farber Cancer Institute
Recruiting
Boston, 02115
Massachusetts
United States
Sarah Cannon Research Institute Drug Ship - 3
Recruiting
Nashville, 37203
Tennessee
United States
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Hong Kong
Novartis Investigative Site
Recruiting
Shatin, New Territories,
-
Hong Kong
Japan
Novartis Investigative Site
Recruiting
Chuo ku, 104 0045
Tokyo
Japan
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]