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

• ClinicalTrials.gov Identifier: NCT03891953
• Recruitment Status: Active, not recruiting
• First Posted: March 27, 2019
• Last Update Posted: April 15, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: March 26, 2019
• First Posted Date: March 27, 2019
• Last Update Posted Date: April 15, 2024
• Actual Study Start Date: May 7, 2019
• Estimated Primary Completion Date: September 12, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 24, 2022)

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

Original Secondary Outcome Measures (submitted: March 26, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors.
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Carcinoma, Non-Small-Cell Lung
• Melanoma
• Nasopharyngeal Carcinoma
• Microsatellite Stable Colorectal Cancer
• Triple Negative Breast Cancer

Intervention

• 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

Study Arms

• Experimental: DKY709
  DKY709 monotherapy
  Intervention: Drug: DKY709
• Experimental: DKY709 + PDR001
  Combination therapy with DKY709 and PDR001
  Interventions:

  • Drug: DKY709
  • Drug: PDR001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 19, 2023): 98
• Original Estimated Enrollment (submitted: March 26, 2019): 320
• Estimated Study Completion Date: September 12, 2024
• Estimated Primary Completion Date: September 12, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Hong Kong, Japan, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03891953
• Other Study ID Numbers: CDKY709A12101C; 2018-002580-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: April 2024