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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03891953

Collaborator

(none)

380

Enrollment

Locations

Arms

59.3

Anticipated Duration (Months)

42.2

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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

Anticipated Primary Completion Date :

Apr 15, 2024

Anticipated Study Completion Date :

Apr 15, 2024

Arms and Interventions

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 Names: Spartalizumab

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 Names:

Spartalizumab

Outcome Measures

Primary Outcome Measures

Safety of DKY709 single agent treatment or DKY709 in combination with PDR001. [24 months]
Incidence and severity of AEs and SAEs
incidence of Dose Limiting Toxicities (DLTs) [1 Month]
The incidence of DLTs during the first cycle of treatment with single agent DKY709 or the combination of DKY709 with PDR001.
Tolerability of DKY709 single agent treatment or DKY709 in combination with PDR001. [24 months]
Incidence and severity of AEs and SAEs

Secondary Outcome Measures

AUC of DKY709 and PDR001 [24 months]
AUC
Cmax of DKY709 and PDR001 [24 months]
Cmax
Tmax of DKY709 and PDR001 [24 months]
Tmax
Half-life of DKY709 and PDR001 [24 months]
Half-life
Progression Free Survival (PFS) [24 months]
Determine PFS in each part of the study
Best Overall Response (BOR) [24 months]
Determine BOR in each part of the study
Duration of Response (DOR) [24 months]
Determine DOR in each part of the study
Time to Progression (TTP) [24 months]
Determine TTP in each part of the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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

ECOG Performance Status ≤ 1
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:

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)
Magnesium, calcium or phosphate abnormality CTCAE > grade 1
Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Massachusetts Gen Hosp	Boston	Massachusetts	United States	02114
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Sarah Cannon Research Institute Drug Ship - 3	Nashville	Tennessee	United States	37203
4	Novartis Investigative Site	Dresden		Germany	01307
5	Novartis Investigative Site	Essen		Germany	45147
6	Novartis Investigative Site	Shatin, New Territories		Hong Kong
7	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104 0045
8	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
9	Novartis Investigative Site	Taipei		Taiwan	10002