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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Carcinoma, Non-Small-Cell Lung; Nasopharyngeal Carcinoma; Triple Negative Breast Cancer; Microsatellite Stable Colorectal Cancer
• Intervention / Treatment: Drug: DKY709; Drug: PDR001

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
• Hong Kong
  • Shatin New Territories, Hong Kong
    • Novartis Investigative Site
• Japan
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Massachusetts Gen Hosp
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Drug Ship - 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Estimated): September 12, 2024
• Study Completion (Estimated): September 12, 2024

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Melanoma; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Microsatellite Stable Colorectal Cancer; Nasopharyngeal Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Nasopharyngeal Neoplasms; Breast Neoplasms; Skin Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Nasopharyngeal Carcinoma; Colorectal Neoplasms; Melanoma; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CDKY709A12101C; 2018-002580-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No