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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03891953

Studienbeginn:
Mai 2019

Letztes Update:
15.07.2020

Wirkstoff:
DKY709, PDR001

Indikation (Clinical Trials):
Carcinoma, Melanoma, Colorectal Neoplasms, Triple Negative Breast Neoplasms, Nasopharyngeal Carcinoma, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations (3 von 6)

Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
Shatin, New Territories
Hong KongRekrutierend» Google-Maps
Novartis Investigative Site
104 0045 Chuo ku
JapanRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Safety of DKY709 single agent treatment or DKY709 in combination with PDR001. (Time Frame - 24 months):
Incidence and severity of AEs and SAEs

2. 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.

3. Tolerability of DKY709 single agent treatment or DKY709 in combination with PDR001. (Time Frame - 24 months):
Incidence and severity of AEs and SAEs

Secondary outcome:

1. AUC of DKY709 and PDR001 (Time Frame - 24 months):
AUC

2. Cmax of DKY709 and PDR001 (Time Frame - 24 months):
Cmax

3. Tmax of DKY709 and PDR001 (Time Frame - 24 months):
Tmax

4. Half-life of DKY709 and PDR001 (Time Frame - 24 months):
Half-life

5. Concentration vs time profile of DKY709 and PDR001 (Time Frame - 24 months):
Concentration vs. time

6. Progression Free Survival (PFS) (Time Frame - 24 months):
Determine PFS in each part of the study

7. Best Overall Response (BOR) (Time Frame - 24 months):
Determine BOR in each part of the study

8. Duration of Response (DOR) (Time Frame - 24 months):
Determine DOR in each part of the study

9. Time to Progression (TTP) (Time Frame - 24 months):
Determine TTP in each part of the study

Studien-Arme

  • Experimental: DKY709
    DKY709 monotherapy
  • Experimental: DKY709 + PDR001
    Combination therapy with DKY709 and PDR001

Geprüfte Regime

  • DKY709:
    Novel immunomodulatory agent
  • PDR001 (Spartalizumab):
    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

Quelle: ClinicalTrials.gov


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