Clinical Trials /

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

NCT03891953

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Melanoma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CDKY709A12101C
  • NCT ID: NCT03891953

Conditions

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

Interventions

DrugSynonymsArms
DKY709DKY709
PDR001SpartalizumabDKY709 + PDR001

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DKY709ExperimentalDKY709 monotherapy
  • DKY709
DKY709 + PDR001ExperimentalCombination therapy with DKY709 and PDR001
  • DKY709
  • PDR001

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

               -  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.

          6. ECOG Performance Status ≤ 2

          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.

        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)

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

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of DKY709 single agent treatment or DKY709 in combination with PDR001.
Time Frame:24 months
Safety Issue:
Description:Incidence and severity of AEs and SAEs

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non-small Cell Lung Cancer, melanoma, Nasopharyngeal Carcinoma, Microsatellite Stable Colorectal Cancer, Triple Negative Breast Cancer

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